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Behlock Y, Dandoy C, Willaert F, Debusscher C, Njimi H, Benhadou F, del Marmol V, White JML. Early Use of Beneficial Biological Therapy on Younger Psoriasis Patients: Could a 'Step-Down' Therapy Approach Be More Effective? Int J Dermatol 2025; 64:1049-1056. [PMID: 39988483 PMCID: PMC12082614 DOI: 10.1111/ijd.17704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 01/31/2025] [Accepted: 02/04/2025] [Indexed: 02/25/2025]
Abstract
INTRODUCTION Psoriasis is a chronic autoimmune skin disorder affecting roughly 2% of the population worldwide. This condition manifests variably due to individual phenotypes. As the number of therapies has increased, Belgium established its own registry. However, these treatments are often inaccessible due to reimbursement criteria. This study suggests that some groups of psoriasis patients (particularly younger patients) may selectively benefit from early treatment approaches with biological therapies. MATERIAL AND METHODS Patients diagnosed with psoriasis included in the Belgian Psoriasis Registry were included in the study. Collected data included socio-demographic changes, lifestyle changes, psoriasis-related characteristics, treatment specifics and treatment changes, and associated diseases. RESULTS Two hundred and five patients were included. Patients were classified as responders if their Psoriasis Area Severity Index (PASI) score decreased by more than 75% between the initial visit and follow-up (PASI75). 47% of patients achieved PASI75. In the short-term, 50% of patients treated with biologic therapy, 30.5% on systemic conventional therapies, and 32.25% on topicals/phototherapy responded with PASI75. At long-term follow-up, an increase in response was observed in patients receiving biologic therapy, as well as in patients undergoing systemic conventional therapy (55.5%). Patients receiving treatment shortly after their first lesions' onset had better responses (p value < 0.0001). CONCLUSION Intervening earlier with effective treatments improves outcomes, particularly in younger patients. Treatment algorithms should use a step-down approach rather than a step-up approach. This would enhance the number of responders and potentially reduce costs.
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Affiliation(s)
- Yasmina Behlock
- Department of DermatologyBrussels University HospitalBrusselsBelgium
| | - Celine Dandoy
- Department of DermatologyBrussels University HospitalBrusselsBelgium
| | - Fabienne Willaert
- Department of DermatologyBrussels University HospitalBrusselsBelgium
| | - Claire Debusscher
- Department of DermatologyBrussels University HospitalBrusselsBelgium
| | - Hassane Njimi
- Department of BiostatisticsBrussels University HospitalBrusselsBelgium
| | - Farida Benhadou
- Department of DermatologyBrussels University HospitalBrusselsBelgium
| | | | - Jonathan M. L. White
- Department of DermatologyBrussels University HospitalBrusselsBelgium
- Ecole de Santé PubliqueUniversité libre de BruxellesBrusselsBelgium
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Sun J, Brooks EC, Houshyar Y, Connor SJ, Paven G, Grimm MC, Hold GL. Unravelling the Relationship Between Obesity and Inflammatory Bowel Disease. Inflamm Bowel Dis 2025:izaf098. [PMID: 40397482 DOI: 10.1093/ibd/izaf098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Indexed: 05/22/2025]
Abstract
Mirroring the global obesity epidemic, obesity rates in inflammatory bowel disease (IBD) patients is rising. Several epidemiological studies propose that 15%-40% of adult patients with IBD are obese, and an additional 25%-40% fall into the overweight category. This article examines the pathophysiologic relationship between obesity and IBD concerning the role of visceral adipose tissue, microbiota shifts, dietary patterns, and hunger hormone changes. Additionally, increasing evidence is demonstrating the negative impact that obesity is having on disease course and quality of life in patients with IBD. Obesity has been demonstrated to be associated with an attenuated response to immunomodulators and biological agents, as well as higher rates of peri-operative surgical complications. A better understanding of the relationship between obesity and IBD can be applied to clinical decision-making in personalizing treatment plans, promoting weight loss in patients with obesity, and identifying areas of future research.
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Affiliation(s)
- Jessica Sun
- Microbiome Research Centre, School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia
- Prince of Wales Hospital, South Eastern Sydney Local Health District, Sydney, NSW, Australia
| | - Ella C Brooks
- Microbiome Research Centre, School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Yashar Houshyar
- Microbiome Research Centre, School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia
- St. George and Sutherland Clinical Campuses, University of New South Wales, Sydney, NSW, Australia
| | - Susan J Connor
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Liverpool, NSW 2170, Australia
| | - Gokulan Paven
- St. George and Sutherland Clinical Campuses, University of New South Wales, Sydney, NSW, Australia
| | - Michael C Grimm
- Microbiome Research Centre, School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia
- St. George and Sutherland Clinical Campuses, University of New South Wales, Sydney, NSW, Australia
| | - Georgina L Hold
- Microbiome Research Centre, School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia
- St. George and Sutherland Clinical Campuses, University of New South Wales, Sydney, NSW, Australia
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Cheon JH, Ye BD, Armuzzi A, Rieder F, Girolomoni G, Puig L, Jung H, Feldman SR. The "totality of evidence" and "extrapolation" of SB17, a ustekinumab biosimilar. Expert Opin Biol Ther 2025. [PMID: 40396611 DOI: 10.1080/14712598.2025.2508838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 04/01/2025] [Accepted: 05/16/2025] [Indexed: 05/22/2025]
Abstract
INTRODUCTION SB17 is a ustekinumab (UST) biosimilar targeting interleukin-12/23 for treating immune-medicated inflammatory diseases (IMIDs). The development of UST biosimilars like SB17 May help address the high cost of innovator biologics, offering affordable alternatives without compromising efficacy or safety. AREAS COVERED This review encompasses the totality of evidence supporting SB17's similarity to UST, its regulatory approval, and indication extrapolation. It also discusses SB17's lower immunogenicity relative to UST. EXPERT OPINION The approval of UST biosimilars represents a significant advancement in managing chronic IMIDs including psoriasis, plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis, providing cost-effective, efficacious alternatives. A randomized double-blind 28-week study involving over 500 patients with moderate-to-severe chronic plaque psoriasis demonstrated SB17's equivalence to UST, with more than 80% of patients achieving over 90% improvement in psoriasis severity indices. Treatment-emergent adverse events were comparable between SB17 and UST. Despite their potential to transform clinical outcomes, economic burdens, and drug utilization patterns, the adoption of UST biosimilars faces challenges, including concerns about equivalence and regulatory inconsistencies. Addressing these issues through education, consistent regulatory frameworks, real-world data, and ongoing monitoring is crucial for their successful integration into clinical practice.
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Affiliation(s)
- Jae Hee Cheon
- Department of Internal Medicine, Yonsei University College of Medicine and Inflammatory Bowel Disease Center, Seoul, South Korea
| | - Byong Duk Ye
- Department of Gastroenterology and Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Alessandro Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital - IRCCS, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Florian Rieder
- Department of Gastroenterology, Hepatology and Nutrition; Digestive Diseases Institute; Cleveland Clinic, Cleveland, OH, USA
| | - Giampiero Girolomoni
- Section of Dermatology, Department of Medicine, University of Verona, Verona, Italy
| | - Luis Puig
- Department of Dermatology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | - Steven R Feldman
- Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
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Wong C, Bassett P, Kamperidis N, Misra R, Younge L, Dyall L, Yeung K, Rejee C, Arebi N. Prolonged time to treatment of biologics in inflammatory bowel disease: disparities from a retrospective study in a tertiary referral centre in the UK. BMC Gastroenterol 2025; 25:352. [PMID: 40346554 PMCID: PMC12063266 DOI: 10.1186/s12876-025-03909-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 04/17/2025] [Indexed: 05/11/2025] Open
Abstract
BACKGROUND Several disparities in healthcare utilisation and delivery are reported in inflammatory bowel disease (IBD). We examined disparities for delays in biologic administration. METHODS This is a tertiary centre, retrospective, cohort study of consecutive adult IBD outpatients referred to the biologics clinic (BC) for initiation of therapy over 2 years. We collected patient-, disease- and service-related data in addition to adverse clinical outcomes (primary non-response, corticosteroid prescription, IBD hospital admission and surgery) within 6 months of the first dose of therapy. The primary outcome was time-to-therapy (TTT): time interval from referral to the first drug dose. Univariate and multivariate regression analyses examined associations between variables and TTT. RESULTS 240 patients started biologics: 87 (36%) ulcerative colitis (UC) and 153 (64%) Crohn's disease (CD). Median referral age was 43 years (IQR 34-56) and 128 (53%) were male. Charlson Comorbidity Index was ≤ 1 in 185 patients (77%) and 141 (59%) were biologic naïve. 91 (37.9%) were White British, 88 (36.7%) Asian (Indian or Pakistani), 61 (25.4%) were from other ethnic groups. Median TTT was 76 (IQR 56-97) days. In multivariable analysis, longer TTT was associated with CD, other ethnic groups and Adalimumab. Lack of funding at the time of BC and referral age were of borderline statistical significance. Adverse outcomes at 6 months was significantly associated with C-reactive protein level > 10 mg/L (OR 2.13; p = 0.03) but not with longer TTT. CONCLUSIONS Delays in initiating biologic therapy are significantly associated with IBD type, ethnicity and therapy type. Unwarranted variation in IBD care can be mitigated by concerted initiatives to address modifiable factors for timely access to effective therapies.
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Affiliation(s)
- Charlotte Wong
- Department of Inflammatory Bowel Disease, St Mark's National Bowel Hospital, London, UK.
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
| | | | - Nikolaos Kamperidis
- Department of Inflammatory Bowel Disease, St Mark's National Bowel Hospital, London, UK
| | - Ravi Misra
- Department of Inflammatory Bowel Disease, St Mark's National Bowel Hospital, London, UK
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Lisa Younge
- Department of Inflammatory Bowel Disease, St Mark's National Bowel Hospital, London, UK
| | - Lovesh Dyall
- Department of Inflammatory Bowel Disease, St Mark's National Bowel Hospital, London, UK
| | - Katie Yeung
- Department of Inflammatory Bowel Disease, St Mark's National Bowel Hospital, London, UK
| | - Christy Rejee
- Department of Inflammatory Bowel Disease, St Mark's National Bowel Hospital, London, UK
| | - Naila Arebi
- Department of Inflammatory Bowel Disease, St Mark's National Bowel Hospital, London, UK
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
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Tianeze de Castro C, da Silva Oliveira D, Freire de Melo F, Lima Barreto M, de Souza Teles Santos CA, Barbosa Dos Santos D. Global prevalence of biologic drugs use in inflammatory bowel diseases: a systematic review and meta-analysis. Scand J Gastroenterol 2025; 60:439-453. [PMID: 40237230 DOI: 10.1080/00365521.2025.2491013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/17/2025] [Accepted: 04/04/2025] [Indexed: 04/18/2025]
Abstract
OBJECTIVES Biologics are increasingly essential in managing inflammatory bowel diseases (IBDs) worldwide, as they can modify disease progression and improve patients' quality of life. This study aimed to analyze the global prevalence of and geographic variations in the use of biological drugs for IBD. MATERIALS AND METHODS Articles published up to 21 July 2024, were identified from the PubMed/MEDLINE, Web of Science, Scopus, Embase, IBECS, WPRIM, BRISA/RedETSA and LILACS databases. Population-based studies (cohort, case-control and cross-sectional) and studies using administrative databases with data on the prevalence of biological medicine use in patients with IBD were included. Two reviewers independently screened the studies, extracted data, and assessed methodological quality. Estimates were pooled using a random-effects meta-analysis, whereas heterogeneity was evaluated using Cochran's Q test and I2. RESULTS Of the 8239 titles, 68 (n = 3,482,385 patients) were included. An increase in the number of studies on the subject has been reported since 2017, and these studies have been mostly concentrated in high-income countries. A 15.06% (95% CI 11.84-18.28%) prevalence of biologic use in IBD worldwide was reported, predominantly concentrated in the use of anti-TNF agents 15.01% (95% CI 10.35-19.67%). Furthermore, patients with Crohn's disease (CD) had a greater prevalence of biologic use (21.41%; 95% CI 16.31-26.50%) than ulcerative colitis (UC) patients (9.70%; 95% CI 6.20-13.18%). CONCLUSIONS Further studies using population-based and administrative data and stratifying their analyses by disease type are required to confirm our findings. Future studies should be conducted in Latin America, Asia and Africa.
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Affiliation(s)
| | | | | | - Mauricio Lima Barreto
- Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
| | - Carlos Antonio de Souza Teles Santos
- Institute of Collective Health, Federal University of Bahia, Salvador, Bahia, Brazil
- Center of Data and Knowledge Integration for Health (CIDACS), Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil
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6
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Boaz E, Ledder O, Bar-Gil Shitrit A, Dagan A, Freund MR, Koslowsky B, Lujan R, Greenfeld S, Kariv R, Loewenberg Weisband Y, Lederman N, Matz E, Dotan I, Turner D, Yellinek S. Ethnic Disparities in the Management of Inflammatory Bowel Disease in Israel and Impact on Outcomes. CROHN'S & COLITIS 360 2025; 7:otaf025. [PMID: 40321840 PMCID: PMC12048840 DOI: 10.1093/crocol/otaf025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Indexed: 05/08/2025] Open
Abstract
Background In this nationwide study, we aimed to explore healthcare services utilization, medical management, and disease outcomes of inflammatory bowel diseases (IBD) across the 2 major ethnic groups in Israel. Methods We utilized a cohort including all patients diagnosed with IBD in Israel since 2005. The primary outcome was steroid dependency, with secondary outcomes including use of biologics, time to surgery, and hospitalizations. Outcomes were controlled for possible inherent differences in disease course and phenotype. Results Of the 32 491 included patients, 18 252 (56%) had Crohn's disease (CD) and 14 239 (44%) had ulcerative colitis (UC); 10% were Arabs and 90% were Jews. Jewish ethnicity was associated with lower rates of steroid dependency compared to Arab ethnicity in both CD (HR = 0.7 [95% CI, 0.6-0.8]) and UC (HR = 0.7 [95% CI, 0.6-0.8]). The risk of IBD-related surgery in CD was higher in the Arab group at both 3 and 5 years (13% vs. 10%, 16% vs 14%, respectively, P = .005). Arabs had more frequent IBD-related hospitalizations than Jews at 5 years (28% vs. 19% with at least 2 hospitalizations, P < .001). In contrast, Jewish ethnicity was associated with more frequent use of biologics during the first year from diagnosis in patients with CD (HR = 1.3 [95% CI, 1.1-1.6]) but not with UC. Conclusions Arab ethnicity is associated with higher rates of hospitalizations, steroid dependency, and surgeries, and, on the other side, with lower utilization of biologics. Healthcare practitioners and policymakers should address potential cultural and systemic barriers in healthcare delivery in order to improve care across all populations.
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Affiliation(s)
- Elad Boaz
- Department of General Surgery, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Oren Ledder
- Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Ariella Bar-Gil Shitrit
- Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Amir Dagan
- Department of General Surgery, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Michael R Freund
- Department of General Surgery, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Benjamin Koslowsky
- Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Rona Lujan
- Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Shira Greenfeld
- Maccabi Health Services, The Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, IsraelTel-Aviv, Israel
- The Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
| | - Revital Kariv
- Maccabi Health Services, The Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, IsraelTel-Aviv, Israel
- The Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
| | | | | | - Eran Matz
- Leumit Health Services, Tel-Aviv, Israel
| | - Iris Dotan
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Dan Turner
- Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Shlomo Yellinek
- Department of General Surgery, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
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Gilmore R, Fernandes R, Schildkraut T, Joshi R, Lin L, Vorgin S, Etchegaray A, Shanmuga Anandan A, Tambakis G, Loebenstein M, An YK, Begun J, Wright EK. The Durability of Anti-TNF Therapy for Crohn's Disease Is Higher in Anti-TNF Naïve Patients and Increases With Proactive Therapeutic Drug Monitoring. CROHN'S & COLITIS 360 2025; 7:otaf028. [PMID: 40321838 PMCID: PMC12048839 DOI: 10.1093/crocol/otaf028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Indexed: 05/08/2025] Open
Abstract
Background Antitumor necrosis factor (TNF) dose escalation is performed to improve therapeutic response and optimize outcomes in patients with Crohn's disease (CD). We aimed to describe the durability of anti-TNF therapy in patients with CD receiving escalated anti-TNF therapy, along with the overall durability of anti-TNF treatment between patients managed with a proactive versus reactive therapeutic drug monitoring (TDM) approach. Methods We undertook a retrospective multicentre cohort study. One center practiced proactive TDM with a weekly virtual TDM clinic, while the other practiced reactive TDM. Patients receiving escalated infliximab or adalimumab therapy for CD from January 2015 to April 2022 were included. Durability was defined as the time from biologic start to cessation for treatment failure. Results About 239 patients (45% female, median age 39) meeting criteria for inclusion were identified. About 165 patients were included in the proactive TDM cohort and 74 in the reactive TDM cohort.Anti-TNF naïve patients had significantly higher durability of therapy when compared with the anti-TNF exposed patients for both overall durability (P = .045) and durability postescalation (P = .017). The proactive TDM cohort had significantly higher durability when compared with the reactive cohort for both overall durability (P = .001) and durability postescalation (P = .002). Conclusions This multicentre, retrospective cohort study illustrates the importance of dose escalation as a therapeutic strategy in IBD care. The durability of anti-TNF therapy is superior in anti-TNF naïve compared to exposed patients and can be improved further by proactive TDM to guide dose optimization.
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Affiliation(s)
- Robert Gilmore
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Australia
- Department of Gastroenterology, Mater Hospital, Brisbane, Australia
- Mater Research Institute, University of Queensland, South Brisbane, Australia
| | - Richard Fernandes
- Department of Gastroenterology, Mater Hospital, Brisbane, Australia
- Mater Research Institute, University of Queensland, South Brisbane, Australia
| | - Tamar Schildkraut
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Australia
| | - Riddhi Joshi
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Australia
| | - Lyman Lin
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Australia
| | - Sara Vorgin
- Department of Medicine, University of Melbourne, Melbourne, Australia
| | | | | | - George Tambakis
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Australia
| | - Moshe Loebenstein
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Australia
| | - Yoon-Kyo An
- Department of Gastroenterology, Mater Hospital, Brisbane, Australia
- Mater Research Institute, University of Queensland, South Brisbane, Australia
| | - Jakob Begun
- Department of Gastroenterology, Mater Hospital, Brisbane, Australia
- Mater Research Institute, University of Queensland, South Brisbane, Australia
| | - Emily K Wright
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Australia
- Department of Medicine, University of Melbourne, Melbourne, Australia
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Demirci S, Sezer S. Serum Maresin-1 and Resolvin-D1 Levels as Non-Invasive Biomarkers for Monitoring Disease Activity in Ulcerative Colitis. Diagnostics (Basel) 2025; 15:834. [PMID: 40218184 PMCID: PMC11988678 DOI: 10.3390/diagnostics15070834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 03/21/2025] [Accepted: 03/24/2025] [Indexed: 04/14/2025] Open
Abstract
Background: Specialized pro-resolving lipid mediators (SPMs), such as maresins and resolvins, play a key role in resolving inflammation and repairing tissues. This study aimed to evaluate whether maresin-1 (MaR1) and resolvin-D1 (RvD1) could serve as serum non-invasive biomarkers for monitoring disease activity in ulcerative colitis (UC). Methods: This cross-sectional study included 60 UC patients (30 active, 30 remission) and 30 healthy controls. Disease activity was assessed using the Mayo Endoscopic Subscore (MES). Inflammatory indices, including the neutrophil-lymphocyte ratio (NLR), monocyte-HDL cholesterol ratio (MHR), platelet-lymphocyte ratio (PLR), CRP-lymphocyte ratio (CLR), CRP-albumin ratio (CAR), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII), were calculated. Plasma MaR1 and RvD1 levels were measured via enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) analysis was performed to evaluate biomarker accuracy. Results: CRP, NLR, PLR, CLR, CAR, SIRI, and SII were significantly elevated in active UC, whereas MaR1 and RvD1 were lower compared to remission and controls (p < 0.05). MaR1 levels were lower in the remission group than in controls. ROC analysis demonstrated high area under the curve (AUC) values for RvD1 (0.906), CAR (0.872), CLR (0.861), and CRP (0.858) in distinguishing active UC from remission, and for CRP (0.944), CAR (0.939), CLR (0.939), RvD1 (0.928), and MaR1 (0.889) in distinguishing active UC from controls. The specificity for detecting active UC was 60% for MaR1 and 80% for RvD1. Both RvD1 and MaR1 showed a negative correlation with the MES, with RvD1 demonstrating a stronger correlation (r = -0.754, p < 0.001). Conclusions: RvD1 shows a strong negative correlation with disease severity in ulcerative colitis, while low MaR1 levels in remission may indicate subclinical inflammation. Although MaR1 and RvD1 are not disease-specific, their role in inflammation resolution suggests they may complement conventional inflammatory markers for more comprehensive UC monitoring.
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Affiliation(s)
- Selim Demirci
- Department of Gastroenterology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, 06200 Ankara, Türkiye;
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Fiorino G, Ananthakrishnan A, Cohen RD, Cross RK, Deepak P, Farraye FA, Halfvarson J, Steinhart AH. Accelerating Earlier Access to Anti-TNF-α Agents with Biosimilar Medicines in the Management of Inflammatory Bowel Disease. J Clin Med 2025; 14:1561. [PMID: 40095484 PMCID: PMC11900083 DOI: 10.3390/jcm14051561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 02/04/2025] [Accepted: 02/24/2025] [Indexed: 03/19/2025] Open
Abstract
Data indicate that earlier initiation of anti-tumor necrosis factor alpha (anti-TNF-α) biologic medicines may prevent progression to irreversible bowel damage and improve outcomes for patients with inflammatory bowel disease (IBD), particularly Crohn's disease. However, the high cost of such therapies may restrict access and prevent timely treatment of IBD. Biosimilar anti-TNF-α medicines may represent a valuable opportunity for cost savings and optimized patient outcomes by improving access to advanced therapies and allowing earlier anti-TNF-α treatment initiation. Biosimilar anti-TNF-α medicines have been shown to offer consistent therapeutic outcomes to their reference medicines, yet despite entering the IBD treatment armamentarium over 10 years ago, their implementation in clinical practice remains suboptimal. Factors limiting the 'real' use of biosimilar anti-TNF-α medicines may include an ongoing lack of understanding and acceptance of biosimilars by both healthcare professionals (HCPs) and patients, as well as systemic factors such as formulary decisions outside of the control of the prescriber. In this review, an expert panel of gastroenterologists discusses HCP-level considerations to improve biosimilar anti-TNF-α utilization in IBD in order to support early anti-TNF-α initiation and maximize patient outcomes.
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Affiliation(s)
| | | | | | - Raymond K. Cross
- The Melissa L. Posner Institute for Digestive Health & Liver Disease at Mercy Medical Center, Baltimore, MD 21202, USA
| | - Parakkal Deepak
- Division of Gastroenterology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA
| | | | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden
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10
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Ballesta-López O, Gil-Candel M, Centelles-Oria M, Megías-Vericat JE, Solana-Altabella A, Ribes-Artero H, Nos-Mateu P, García-Pellicer J, Poveda-Andrés JL. Pharmacogenetics in Response to Biological Agents in Inflammatory Bowel Disease: A Systematic Review. Int J Mol Sci 2025; 26:1760. [PMID: 40004223 PMCID: PMC11855474 DOI: 10.3390/ijms26041760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 02/07/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders influenced by microbial, environmental, genetic, and immune factors. The introduction of biological agents has transformed IBD therapy, improving symptoms, reducing complications, and enhancing patients' quality of life. However, approximately 30% of patients exhibit primary non-response, and 50% experience a loss of response over time. Genetic and non-genetic factors contribute to variability in treatment outcomes. This systematic review aims to thoroughly analyze and assess existing studies exploring the relationships between genetic variations and individual responses to biologic drugs, in order to identify genetic markers that are predictive of treatment efficacy, risk of adverse effects, or drug toxicity, thereby informing clinical practice and guiding future research. PubMed and EMBASE papers were reviewed by three independent reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] guidelines. Of the 883 records screened, 99 met the inclusion criteria. The findings of this review represent an initial step toward personalized medicine in IBD, with the potential to improve clinical outcomes in biological therapy.
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Affiliation(s)
- Octavio Ballesta-López
- Pharmacy Department, Hospital Universitari i Politècnic La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain; (O.B.-L.)
- Accredited Research Group on Pharmacy, Instituto de Investigación Sanitaria La Fe (IISLAFE), Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
| | - Mayte Gil-Candel
- Pharmacy Department, Hospital Universitari i Politècnic La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain; (O.B.-L.)
- Accredited Research Group on Pharmacy, Instituto de Investigación Sanitaria La Fe (IISLAFE), Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
| | - María Centelles-Oria
- Pharmacy Department, Hospital Universitari i Politècnic La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain; (O.B.-L.)
- Accredited Research Group on Pharmacy, Instituto de Investigación Sanitaria La Fe (IISLAFE), Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
| | - Juan Eduardo Megías-Vericat
- Pharmacy Department, Hospital Universitari i Politècnic La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain; (O.B.-L.)
- Accredited Research Group on Pharmacy, Instituto de Investigación Sanitaria La Fe (IISLAFE), Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
| | - Antonio Solana-Altabella
- Pharmacy Department, Hospital Universitari i Politècnic La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain; (O.B.-L.)
- Accredited Research Group on Pharmacy, Instituto de Investigación Sanitaria La Fe (IISLAFE), Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
- Accredited Research Group on Hematology, Instituto de Investigación Sanitaria La Fe (IISLAFE), Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
| | - Hugo Ribes-Artero
- Pharmacy Department, Hospital Universitari i Politècnic La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain; (O.B.-L.)
- Accredited Research Group on Pharmacy, Instituto de Investigación Sanitaria La Fe (IISLAFE), Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
| | - Pilar Nos-Mateu
- Inflammatory Bowel Disease Unit, Gastroenterology Department, Hospital Universitari i Politècnic La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
| | - Javier García-Pellicer
- Pharmacy Department, Hospital Universitari i Politècnic La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain; (O.B.-L.)
- Accredited Research Group on Pharmacy, Instituto de Investigación Sanitaria La Fe (IISLAFE), Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
| | - José Luis Poveda-Andrés
- Pharmacy Department, Hospital Universitari i Politècnic La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain; (O.B.-L.)
- Accredited Research Group on Pharmacy, Instituto de Investigación Sanitaria La Fe (IISLAFE), Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
- Management Department, Hospital Universitari i Politècnic La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
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Kim EJ, Jeong HS, Park JY, Je JY, Choi CH, Lee SJ. The inflammatory bowel disease and gut microbiome are restored by employing metformin-loaded alginate-shelled microcapsules. J Control Release 2025; 378:490-502. [PMID: 39710207 DOI: 10.1016/j.jconrel.2024.12.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 12/12/2024] [Accepted: 12/17/2024] [Indexed: 12/24/2024]
Abstract
Inflammatory bowel disease (IBD) is a chronic or recurrent inflammatory disorder affecting various parts of the gastrointestinal tract. Metformin, a widely prescribed hypoglycemic drug for type 2 diabetes, has shown potential in reducing IBD risk. However, its oral administration faces significant challenges due to the harsh gastrointestinal environment, requiring higher or more frequent doses to achieve therapeutic effects, which increases the risk of side effects. To address this, we developed alginate-shelled hydrogel microcapsules with a thin oil layer for targeted intestinal delivery of metformin. The oil layer protects metformin from gastric acid and ensures its release specifically in the intestines. In a dextran sulfate sodium-induced colitis mouse model, metformin-loaded hydrogel microcapsules (MHM) significantly reduced disease activity, intestinal epithelial damage, and macrophage infiltration linked to pro-inflammatory cytokine factors. Additionally, MHM improved dysbiosis of specific bacterial genera, including Bacteroides vulgatus, Lactobacillus (L.) gasseri, L. reuteri, and L. intestinalis, optimizing the abundance and composition of microorganisms. These findings indicate that encapsulating metformin within alginate shelled-microcapsules with a thin oil layer presents a potential delivery system for IBD treatment.
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Affiliation(s)
- Eun-Ju Kim
- Department of Pharmaceutical Engineering, Daegu Haany University, Gyeongsan 38610, Republic of Korea; Major of Human Bio-convergence, Division of Smart Healthcare, Pukyong National University, Busan 48513, Republic of Korea
| | - Hye-Seon Jeong
- School of Chemical Engineering, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea
| | - Ji-Yeon Park
- Major of Human Bio-convergence, Division of Smart Healthcare, Pukyong National University, Busan 48513, Republic of Korea
| | - Jae-Young Je
- Major of Human Bio-convergence, Division of Smart Healthcare, Pukyong National University, Busan 48513, Republic of Korea
| | - Chang-Hyung Choi
- School of Chemical Engineering, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea
| | - Sei-Jung Lee
- Major of Human Bio-convergence, Division of Smart Healthcare, Pukyong National University, Busan 48513, Republic of Korea.
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Hussain FS, Potlach T, Chi X, Gurka MJ, Hall J, Setya A, Chaudhry NA, Pham A, Damas OM, Kerman D, Abreu MT, Zimmermann EM. Healthcare Utilization and Geographic Distribution of Advanced Therapy in Minority Race and Ethnic Groups With Inflammatory Bowel Disease. Inflamm Bowel Dis 2025; 31:344-350. [PMID: 39321098 DOI: 10.1093/ibd/izae219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Indexed: 09/27/2024]
Abstract
BACKGROUND AND AIMS Biases in healthcare pose challenges for inflammatory bowel disease (IBD) patients from underrepresented races and ethnicities. Our study aimed to assess the quality of and access to care among underrepresented racial and ethnic populations using a diverse database. METHODS We used the OneFlorida Data Trust, representing over half of Florida's population. We performed a retrospective study from 2012 to 2020. Advanced IBD therapies included a prescription of at least 1 biologic agent or tofacitinib. Disease activity markers included C-reactive protein (CRP), hemoglobin (Hgb), albumin, and white blood cell (WBC). Regression analyses compared the rates of medication use, healthcare utilization, and disease severity by race and ethnicity. Geographic distribution of advanced IBD therapy was analyzed at the county level. RESULTS Our study included 10 578 patients. Hispanic patients utilized more biologics than non-Hispanic White (NHW) patients (odds ratio [OR]: 1.3, P < .0001). Non-Hispanic Black patients utilized more steroids than NHW (OR: 1.2, P = .0004). Hispanics had fewer visits to emergency departments (EDs) and fewer admissions compared with NHW (OR: 0.7 and 0.6, respectively; P < .0001). Non-Hispanic Black patients visited ED more frequently than NHW patients (OR: 1.3, P < .0001). Hispanics had lower disease activity markers than NHW based on CRP (OR: 0.5, P = .005), Hgb (OR: 0.4, P < .0001), albumin (OR: 0.7, P < .0001), and WBC (OR: 0.5, P < .0001). Geographic distribution of advanced IBD therapy showed clustered areas in southern and northern Florida. CONCLUSIONS Our data show an improved access to care pattern in Hispanic patients. However, disparities still exist, and this is evident in the healthcare utilization trends observed among non-Hispanic Black patients.
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Affiliation(s)
| | - Tomas Potlach
- College of Medicine, University of Florida, Gainesville, FL, USA
| | - Xiaofei Chi
- Department of Health Outcomes & Biomedical Informatics, University of Florida, Gainesville, FL, USA
| | - Matthew J Gurka
- Department of Health Outcomes & Biomedical Informatics, University of Florida, Gainesville, FL, USA
| | - Jaclyn Hall
- Department of Health Outcomes & Biomedical Informatics, University of Florida, Gainesville, FL, USA
| | - Aniruddh Setya
- Department of Pediatrics, University of Florida, Gainesville, FL, USA
| | | | - Angela Pham
- Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Oriana M Damas
- Department of Medicine, University of Miami, Miami, FL, USA
| | - David Kerman
- Department of Medicine, University of Miami, Miami, FL, USA
| | - Maria T Abreu
- Department of Medicine, University of Miami, Miami, FL, USA
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Chang YC, Chuang CH, Huang TY, Chung CS, Kuo CJ, Pan YB, Le PH. Early Ustekinumab Use Improves Clinical Outcomes in Biologic-Naive Crohn's Disease Patients: A Retrospective Multicenter Cohort Study in Taiwan. Biomedicines 2025; 13:391. [PMID: 40002805 PMCID: PMC11852605 DOI: 10.3390/biomedicines13020391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 02/03/2025] [Accepted: 02/04/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: Crohn's disease (CD) is a progressive condition, and early treatment with infliximab combined with an immunosuppressant within six months has been shown to improve clinical outcomes. However, the impact of early ustekinumab (UST) use in biologic-naïve CD patients remains unclear. This study aims to address this gap by evaluating the clinical outcomes of early UST intervention in such patients. Methods: In this retrospective cohort study, we included biologic-naïve CD patients treated with UST, with a clinical follow-up period of at least six months from October 2020 to January 2024 across four medical centers. Patients who received UST within six months of CD diagnosis were categorized into the Early-UST group, while those who were initially treated with conventional therapies and subsequently received UST after six months were assigned to the control group. The primary endpoint was the improvement of clinical outcomes at six months. Results: A total of 60 biologic-naïve CD patients were enrolled. Baseline characteristics were comparable between the two groups. At six months, the Early-UST group (n = 24) demonstrated significantly lower Crohn's Disease Activity Index (CDAI) scores (73.03 vs. 112.42, p = 0.038), lower Harvey-Bradshaw Index (HBI) scores (1.46 ± 1.69 vs. 2.72 ± 2.17, p = 0.020), higher rates of clinical remission (91.7% vs. 63.9%, p = 0.017), and higher rates of steroid-free clinical remission (79.2% vs. 50.0%, p = 0.031) compared to the control group (n = 36). At one year, the early-UST group continued to exhibit lower CDAI scores (39.94 vs. 91.48, p = 0.005). Conclusions: Initiating ustekinumab within six months of CD diagnosis is associated with improved clinical outcomes and enhanced quality of life in biologic-naïve Crohn's disease patients.
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Affiliation(s)
- Yen-Cheng Chang
- School of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
| | - Chiao-Hsiung Chuang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan;
- Taiwan Association for the Study of Intestinal Diseases (TASID), Taoyuan 333, Taiwan; (T.-Y.H.); (C.-S.C.); (C.-J.K.)
| | - Tien-Yu Huang
- Taiwan Association for the Study of Intestinal Diseases (TASID), Taoyuan 333, Taiwan; (T.-Y.H.); (C.-S.C.); (C.-J.K.)
- Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
| | - Chen-Shuan Chung
- Taiwan Association for the Study of Intestinal Diseases (TASID), Taoyuan 333, Taiwan; (T.-Y.H.); (C.-S.C.); (C.-J.K.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan
| | - Chia-Jung Kuo
- Taiwan Association for the Study of Intestinal Diseases (TASID), Taoyuan 333, Taiwan; (T.-Y.H.); (C.-S.C.); (C.-J.K.)
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan
- Chang Gung Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan
| | - Yu-Bin Pan
- Biostatistical Section, Clinical Trial Center, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan;
| | - Puo-Hsien Le
- Taiwan Association for the Study of Intestinal Diseases (TASID), Taoyuan 333, Taiwan; (T.-Y.H.); (C.-S.C.); (C.-J.K.)
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan
- Chang Gung Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan
- Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan
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Kiilerich KF, Andresen T, Darbani B, Gregersen LHK, Liljensøe A, Bennike TB, Holm R, Moeller JB, Andersen V. Advancing Inflammatory Bowel Disease Treatment by Targeting the Innate Immune System and Precision Drug Delivery. Int J Mol Sci 2025; 26:575. [PMID: 39859291 PMCID: PMC11765494 DOI: 10.3390/ijms26020575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 01/04/2025] [Accepted: 01/09/2025] [Indexed: 01/27/2025] Open
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Current immune-modulating therapies are insufficient for 30-50% of patients or cause significant side effects, emphasizing the need for new treatments. Targeting the innate immune system and enhancing drug delivery to inflamed gut regions are promising strategies. Neutrophils play a central role in IBD by releasing reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) -DNA-based structures with cytotoxic proteins-that contribute to mucosal damage and inflammation. Recent studies linking ROS production, DNA repair, and NET formation have identified NETs as potential therapeutic targets, with preclinical models showing positive outcomes from NET inhibition. Innovative oral drug delivery systems designed to target gut inflammation directly-without systemic absorption-could improve treatment precision and reduce side effects. Advanced formulations utilize properties such as particle size, surface modifications, and ROS-triggered release to selectively target the distal ileum and colon. A dual strategy that combines a deeper understanding of IBD pathophysiology to identify inflammation-related therapeutic targets with advanced drug delivery systems may offer significant promise. For instance, pairing NET inhibition with ROS-responsive nanocarriers could enhance treatment efficacy, though further research is needed. This synergistic approach has the potential to greatly improve outcomes for IBD patients.
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Affiliation(s)
- Kat F. Kiilerich
- Department of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark; (K.F.K.); (J.B.M.)
| | - Trine Andresen
- Department of Health Science and Technology, The Faculty of Medicine, Aalborg University, 9220 Aalborg Ø, Denmark; (T.A.); (T.B.B.)
| | - Behrooz Darbani
- Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark; (B.D.); (L.H.K.G.); (A.L.)
| | - Laura H. K. Gregersen
- Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark; (B.D.); (L.H.K.G.); (A.L.)
- Department of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark
| | - Anette Liljensøe
- Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark; (B.D.); (L.H.K.G.); (A.L.)
| | - Tue B. Bennike
- Department of Health Science and Technology, The Faculty of Medicine, Aalborg University, 9220 Aalborg Ø, Denmark; (T.A.); (T.B.B.)
- Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark; (B.D.); (L.H.K.G.); (A.L.)
| | - René Holm
- Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5000 Odense, Denmark;
| | - Jesper B. Moeller
- Department of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark; (K.F.K.); (J.B.M.)
- Danish Institute for Advanced Study, University of Southern Denmark, 5000 Odense, Denmark
| | - Vibeke Andersen
- Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark; (B.D.); (L.H.K.G.); (A.L.)
- Department of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark
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15
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Johnson WM, Vaughn BP, Lim N. Diagnosis and management of de novo inflammatory bowel disease after solid organ transplantation in the era of biologic therapy: a case series. FRONTIERS IN TRANSPLANTATION 2025; 3:1483943. [PMID: 39846032 PMCID: PMC11751014 DOI: 10.3389/frtra.2024.1483943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 12/23/2024] [Indexed: 01/24/2025]
Abstract
Introduction The clinical characteristics of de novo inflammatory bowel disease (dnIBD) diagnosed after solid organ transplant (SOT) are not well-described, particularly since the advent of biologic therapy for treatment of IBD. Methods We conducted a single-center, retrospective review of SOT recipients between 2010 and 2022 at the University of Minnesota Medical Center who were diagnosed with IBD after transplant. Results Of 89 patients at our center with IBD and a history of SOT, five (5.6%) patients were diagnosed with IBD post-transplant (three liver, one kidney, and one simultaneous liver and kidney): three patients were female and four were Caucasian. Mean age at transplant and IBD diagnosis were 46.7 and 49.4 years respectively. Indication for transplant were alcohol-related cirrhosis (n = 2), idiopathic fulminant hepatic failure (n = 1), metabolic dysfunction-associated steatotic liver disease (n = 1), and IgA nephropathy (n = 1). Four patients were diagnosed with ulcerative colitis (UC) and one with Crohn's disease (CD). Three patients (all with UC) required escalation to a biologic therapy. Four patients were in clinical remission from IBD at last follow-up, one patient required IBD surgery, while there was no rejection and no deaths following IBD diagnosis. Conclusion dnIBD post-SOT is uncommon, while newer IBD therapies may be safe and effective. Further study is required to better understand the natural history and IBD outcomes of this population relative to non-SOT patients.
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Affiliation(s)
| | - Byron P. Vaughn
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, United States
| | - Nicholas Lim
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, United States
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Ui-Haq Z, Causin L, Kamalati T, Kahol D, Vaikunthanathan T, Wong C, Arebi N. Health-care resource use and costs associated with inflammatory bowel disease in northwest London: a retrospective linked database study. BMC Gastroenterol 2024; 24:480. [PMID: 39736541 DOI: 10.1186/s12876-024-03559-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Accepted: 12/10/2024] [Indexed: 01/01/2025] Open
Abstract
BACKGROUND With 20-40% of patients who have inflammatory bowel disease (IBD) not responding to therapy, resource use and costs can be high. We performed a descriptive analysis of health-care data for IBD management in the National Health Service to explore potential areas for improvement. METHODS In this exploratory study, we analysed real-world data from the Discover dataset for adults with a diagnosis of incident IBD recorded in northwest London, UK, between 31 March, 2016, and 31 March, 2020. We compared mean visit numbers and primary and secondary care costs per patient to examine resource use and costs for active disease versus remission. RESULTS We included 7,733 patients (5,872 with ulcerative colitis [UC], 1,427 with Crohn's disease [CD], and 434 with codes for both [termed IBD-undefined in this study]). Remission was recorded in 19,218 (82%) of 23,488 observations for UC, 4,686 (82%) of 5,708 for CD, and 1,122 (65%) for IBD-undefined observations. Health-care resource use was significantly higher with active disease in all settings except primary care for UC. Total health-care costs were greater with active disease than remission for all diagnoses (all p < 0.0001). The main driver of costs was inpatient hospital care among those with active disease; elective inpatient costs were high among patients with UC and IBD-undefined in remission. CONCLUSIONS Higher health-care resource use and costs were observed with active disease, which underscores the importance of early induction and maintenance of remission in UC and CD. Updated strategies that incorporate treat to target may offer cost benefits by the offsetting of biologic drug costs with a reduction in costly inpatient hospital stays. TRIAL REGISTRATION This trial was not registered as it used pseudonymised retrospective data.
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Affiliation(s)
- Zia Ui-Haq
- Imperial College Health Partners, London, UK
| | | | | | | | | | - Charlotte Wong
- Department of Inflammatory Bowel Disease, St Mark's National Bowel Hospital, Central Middlesex Hospital, Acton Lane, London, NW10 7NS, UK
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Naila Arebi
- Department of Inflammatory Bowel Disease, St Mark's National Bowel Hospital, Central Middlesex Hospital, Acton Lane, London, NW10 7NS, UK.
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
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González-Muñoza C, Gely C, Gordillo J, Calafat M, Bertoletti F, Cañete F, Mañosa M, López-Faba A, Torres P, Domènech E, Garcia-Planella E. Perception of the impact of intravenous biological treatment on the work and professional environment in patients with inflammatory bowel disease. GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:502193. [PMID: 38723767 DOI: 10.1016/j.gastrohep.2024.502193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 04/08/2024] [Accepted: 04/12/2024] [Indexed: 06/02/2024]
Abstract
INTRODUCTION In the treatment of inflammatory bowel disease (IBD), we have biologic therapies administered intravenously and subcutaneously. Recently, some drugs can be administered by either of these routes. The real impact that intravenous administration has on the perception of the disease and the personal and work life of the patient is unknown. METHODS All IBD patients receiving intravenous infliximab treatment for at least 6 months were anonymously invited to participate. They were provided with a specific structured questionnaire with visual analogue scales (0-10) at two reference centers in the Barcelona area. RESULTS A total of 90 patients with a median age of 45 years (36-56) and a median infliximab treatment duration of 48 months (24-84) were included. The visit and therapy with infliximab in the day hospital were globally well evaluated (9, IQR 7-10). 78% of patients combined day hospital stays with other activities (26% employment). The personal impact was generally low (4, IQR 0-5.8), but the patient's job was threatened in 43% of patients on intensified treatment. CONCLUSIONS The intravenous administration of biologic drugs on an outpatient basis is highly satisfactory among IBD patients. The impact on the work sphere appears to be more pronounced than on the personal sphere, an aspect that should be considered in shared decision-making with the patient.
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Affiliation(s)
| | - Cristina Gely
- Servicio de Patología Digestiva, Hospital Santa Creu i Sant Pau, Barcelona, España
| | - Jordi Gordillo
- Servicio de Patología Digestiva, Hospital Santa Creu i Sant Pau, Barcelona, España
| | - Margalida Calafat
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - Federico Bertoletti
- Servicio de Patología Digestiva, Hospital Santa Creu i Sant Pau, Barcelona, España
| | - Fiorella Cañete
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - Míriam Mañosa
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - Alberto López-Faba
- Servicio de Patología Digestiva, Hospital Santa Creu i Sant Pau, Barcelona, España
| | - Paola Torres
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Barcelona, España
| | - Eugeni Domènech
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Departamento de Medicina, Universitat Autònoma de Barcelona, Barcelona, España
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Cheifetz AS, Allegretti JR, Quintas M, Dixit B, Farquhar R, Miller BW, Murphy CK, Hershberger E, Ghahramani P, Stevens AC. Small-Molecule Neutrophil Modulator ADS051 is Safe and Well-Tolerated in a Phase 1 Single Ascending Dose Study. Am J Gastroenterol 2024:00000434-990000000-01463. [PMID: 39588987 DOI: 10.14309/ajg.0000000000003237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 10/11/2024] [Indexed: 11/27/2024]
Abstract
INTRODUCTION A need for better treatment options for moderate to severe ulcerative colitis (UC) persists because of the efficacy and safety limitations of current therapies. Neutrophil epithelial transmigration is associated with the characteristic colonic mucosal inflammation in and very likely involved with the pathogenesis and clinical symptoms of UC. ADS051 is a small-molecule inhibiting neutrophil migration and activation, which are potentially important therapeutic targets in UC. The phase 1 single ascending dose study evaluated ADS051's safety, tolerability, and pharmacokinetics in healthy volunteers. METHODS Fifty healthy adults were randomized 4:1 into 5 ascending dose cohorts to receive a single oral dose of ADS051 100 mg, 300 mg, 700 mg, 1,500 mg, 3,500 mg, or placebo. Participants were followed until 30 days after dosing. Safety and pharmacokinetics of ADS051 in stool, blood, and urine were evaluated. RESULTS ADS051 was safe and well-tolerated. Adverse events (AEs) of constipation were reported by 2 participants (5.0%) in the ADS051 1,500 mg group vs none in the placebo group. No serious AEs reported and no discontinuations due to AEs. In all dose groups, a cumulative average of 10%-24% of the ADS051 dose was recovered in stool, mostly within 48 hours after dosing. ADS051 was quantifiable in only 2 of 440 blood samples (7.64 and 69.8 ng/mL). On average, <0.035% of the ADS051 dose was excreted in urine. DISCUSSION ADS051 was safe, well-tolerated, and achieved high stool concentrations with minimal systemic exposure. ADS051 could be a safe and effective, locally acting, neutrophil-targeting agent for the treatment of UC.
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Affiliation(s)
- Adam S Cheifetz
- Harvard Medical School, Boston, Massachusetts, USA
- Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Jessica R Allegretti
- Harvard Medical School, Boston, Massachusetts, USA
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Megan Quintas
- Adiso Therapeutics, Inc., Concord, Massachusetts, USA
| | - Bharat Dixit
- Adiso Therapeutics, Inc., Concord, Massachusetts, USA
| | | | | | | | | | | | - A C Stevens
- Adiso Therapeutics, Inc., Concord, Massachusetts, USA
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Qui M, Salazar E. Beyond Suppression: Peripheral T Cell Responses to Vaccination in Inflammatory Bowel Disease Patients Undergoing Anti-Tumor-Necrosis-Factor Therapy. Vaccines (Basel) 2024; 12:1280. [PMID: 39591183 PMCID: PMC11599089 DOI: 10.3390/vaccines12111280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Revised: 10/29/2024] [Accepted: 11/12/2024] [Indexed: 11/28/2024] Open
Abstract
Alimentary tract inflammation in inflammatory bowel disease (IBD) is treated by systemically administered drugs that alter fundamental host immune responses. Biologics that target tumor necrosis factor (TNF) are first-line biologics in IBD, used widely for their effectiveness, steroid-sparing quality, and lower cost. While they enable a significant proportion of patients to achieve clinical remission, they carry an increased risk of infection and poor serological responses to vaccination. Conversely, our understanding of adaptive T cell responses in anti-TNF-treated IBD patients remains limited. The introduction of COVID-19 vaccines has prompted research that both challenges and refines our view on immunomodulatory therapy and its potential implications for immunity and protection. Here, we review these emergent findings, evaluate how they shape our understanding of vaccine-induced T cell responses in the context of anti-TNF therapy in IBD, and provide a perspective highlighting the need for a holistic evaluation of both cellular and humoral immunity in this population.
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Affiliation(s)
- Martin Qui
- Duke-NUS Medical School, Singapore 169857, Singapore
| | - Ennaliza Salazar
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore 169608, Singapore
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20
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Sun L, Zhao Q, Ao S, Liu T, Wang Z, You J, Mi Z, Sun Y, Xue X, Ogese MO, Gardner J, Meng X, Naisbitt DJ, Liu H, Zhang F. Feedback regulation of VISTA and Treg by TNF-α controls T cell responses in drug allergy. Allergy 2024. [PMID: 39526799 DOI: 10.1111/all.16393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 10/08/2024] [Accepted: 10/16/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Severe cutaneous adverse reactions (SCARs) mediated by cytotoxic T lymphocytes are a series of life-threatening conditions with a mortality of 4%-20%. The clinical application of tumor necrosis factor-alpha (TNF-α) antagonist improves the outcome of some SCARs patients; however, this is complicated by the elusive and varied immunopathogenesis. AIM To investigate whether IgE antibody responses to HEMAs are associated with AD, its severity, and response to dupilumab. METHODS To clarify the precise process and optimize the therapy regimen of SCARs, we performed single-cell sequencing, in vitro functional and clinical analysis of patients with SCARs. RESULTS We observed that TNF-α breaks drug-specific T-cell tolerance by inhibiting the expression of V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA). Furthermore, TNF-α generated a positive feedback loop in the early phase of drug-specific T-cell activation, whereby B cells acted reciprocally on the corresponding T cells to reinforce TNF-α cytokine expression. In contrast, this pathway of TNF-α-VISTA signaling did not operate in memory effector T cells. Drug-specific memory effector T-cell responses were inhibited by increasing Treg cell expression in a negative feedback loop, with TNF-α antagonists preventing the inhibitory effect. These observations align with the clinical analysis that early but not late intervention with TNF-α antagonists significantly improved outcomes in SCARs patients. CONCLUSION Our findings defining feedback regulation of VISTA and Treg cells by TNF-α in different stages of the drug-specific T-cell response and, indicate that a Treg agonists, instead of TNF-α antagonists, could be used for treatment of patients with progressive SCARs.
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Affiliation(s)
- Lele Sun
- Hospital for Skin Diseases, Shandong First Medical University, Jinan, Shandong, China
- Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Qing Zhao
- Hospital for Skin Diseases, Shandong First Medical University, Jinan, Shandong, China
- Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Suiting Ao
- Hospital for Skin Diseases, Shandong First Medical University, Jinan, Shandong, China
- Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Tingting Liu
- Hospital for Skin Diseases, Shandong First Medical University, Jinan, Shandong, China
- Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Zhenzhen Wang
- Hospital for Skin Diseases, Shandong First Medical University, Jinan, Shandong, China
- Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Jiabao You
- Hospital for Skin Diseases, Shandong First Medical University, Jinan, Shandong, China
- Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Zihao Mi
- Hospital for Skin Diseases, Shandong First Medical University, Jinan, Shandong, China
- Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yonghu Sun
- Hospital for Skin Diseases, Shandong First Medical University, Jinan, Shandong, China
- Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Xiaotong Xue
- Hospital for Skin Diseases, Shandong First Medical University, Jinan, Shandong, China
- Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Monday O Ogese
- MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutic, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Joshua Gardner
- MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutic, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Xiaoli Meng
- MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutic, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Dean J Naisbitt
- MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutic, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Hong Liu
- Hospital for Skin Diseases, Shandong First Medical University, Jinan, Shandong, China
- Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China
- School of Public Health, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Furen Zhang
- Hospital for Skin Diseases, Shandong First Medical University, Jinan, Shandong, China
- Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China
- School of Public Health, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
- Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
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21
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Kochhar GS, Khataniar H, Hashash JG, Tabaku F, Regueiro M, Farraye FA, Desai A. Comparative Effectiveness of Ozanimod and Vedolizumab as First-Line Advanced Therapies in Ulcerative Colitis: A Propensity-Matched Cohort Analysis. Inflamm Bowel Dis 2024:izae251. [PMID: 39478367 DOI: 10.1093/ibd/izae251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Indexed: 12/28/2024]
Abstract
INTRODUCTION There is limited real-world evidence comparing the effectiveness of ozanimod to vedolizumab as first-line advanced therapies in patients with ulcerative colitis (UC). METHODS We conducted a retrospective cohort study using TriNetX, a multi-institutional US database in adults with UC who were initiated on ozanimod compared to vedolizumab between January 1, 2021 and 22 June, 2024. The primary outcome was to compare the risk of a composite outcome of corticosteroid use, colectomy, or change to another advanced therapy between the 2 cohorts within 12 months. 1:1 propensity score matching (PSM) was performed for demographics, comorbid conditions, disease extent, laboratory parameters, and previous corticosteroid use. The risk was expressed as an adjusted odds ratio (aOR) with 95% CIs. RESULTS We identified 222 patients in the ozanimod cohort (mean age 41.2 ± 15.7, 46.3% male sex, 68% White, and 22.5% ulcerative proctitis), and 4145 patients in the vedolizumab cohort (mean age 47.4 ± 18.3, 45.2% male sex, 69.7% White, and 17.2% ulcerative proctitis). After PSM, there was no significant difference in the risk of the composite outcome (aOR 0.92, 95% CI, 0.63-1.36) and corticosteroid use (aOR 0.80, 95% CI, 0.53-1.18) between the 2 cohorts within 12 months. There was a higher risk of change in therapy in the ozanimod cohort (aOR 1.95, 95% CI, 1.09-3.49) compared to the vedolizumab cohort. Colectomy rates were low in both cohorts (<0.04%). CONCLUSIONS Our real-world study showed that ozanimod use is associated with similar corticosteroid use but higher odds of a change in therapy compared to vedolizumab when used as first-line therapy in patients with UC. Further prospective studies are needed to understand long-term outcomes.
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Affiliation(s)
- Gursimran S Kochhar
- Division of Gastroenterology, Hepatology & Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
| | - Himsikhar Khataniar
- Department of Internal Medicine, Allegheny Health Network, Pittsburgh, PA, USA
| | - Jana G Hashash
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Fjona Tabaku
- Division of Gastroenterology, Hepatology & Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
| | - Miguel Regueiro
- Division of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Francis A Farraye
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Aakash Desai
- Division of Gastroenterology, Hepatology & Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
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Wahnou H, Hmimid F, Errami A, Nait Irahal I, Limami Y, Oudghiri M. Integrating ADMET, enrichment analysis, and molecular docking approach to elucidate the mechanism of Artemisia herba alba for the treatment of inflammatory bowel disease-associated arthritis. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2024; 87:836-854. [PMID: 39028276 DOI: 10.1080/15287394.2024.2379856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/20/2024]
Abstract
Inflammatory Bowel Disease-Associated Arthritis (IBD-associated arthritis) poses a significant challenge, intertwining the complexities of both inflammatory bowel disease (IBD) and arthritis, significantly compromising patient quality of life. While existing medications offer relief, these drugs often initiate adverse effects, necessitating the requirement for safer therapeutic alternatives. Artemisia herba-alba, a traditional medicinal plant known for its anti-inflammatory properties, emerges as a potential candidate. Our computational study focused on examining 20 bioactive compounds derived from A. herba-alba for potential treatment of IBD-associated arthritis. These compounds detected in A. herba-alba include camphor, alpha-thujone, eucalyptol, cis-chrysanthenyl acetate, vicenin-2, 4,5-di-O-caffeoylquinic acid, chlorogenic acid, hispidulin, isoschaftoside, isovitexin, patuletin-3-glucoside, vanillic acid, rutin, schaftoside, lopinavir, nelfinavir, quercetin, artemisinin, gallic acid, and cinnamic acid. Following rigorous analysis encompassing pharmacokinetics, toxicity profiles, and therapeutic targets, compounds with favorable, beneficial characteristics were identified. In addition, comparative analysis with disease-gene associations demonstrated the interconnectedness of inflammatory pathways across diseases. Molecular docking studies provided mechanistic insights indicating this natural plant components potential to modulate critical inflammatory pathways. Overall, our findings indicate that A. herba-alba-derived compounds may be considered as therapeutic agents for IBD-associated arthritis, warranting further experimental validation and clinical exploration.
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Affiliation(s)
- Hicham Wahnou
- Laboratory of Immunology and Biodiversity, Faculty of Sciences Ain Chock, Hassan II University, Casablanca, Morocco
| | - Fouzia Hmimid
- Laboratoire Santé et Environnement, Faculté des Sciences Ain Chock, Université Hassan II de Casablanca, Casablanca, Morocco
- Équipe de Biotechnologie, Environnement et Santé, Faculté des Sciences El Jadida, Université Chouaïb Doukkali, El Jadida, Morocco
| | - Ahmed Errami
- Laboratoire de Génie des Procédés et de l'Environnement, École Supérieure de Technologie, Université Hassan II de Casablanca, El Jadida, Morocco
| | - Imane Nait Irahal
- Laboratoire Santé et Environnement, Faculté des Sciences Ain Chock, Université Hassan II de Casablanca, Casablanca, Morocco
| | - Youness Limami
- Laboratory of Immunology and Biodiversity, Faculty of Sciences Ain Chock, Hassan II University, Casablanca, Morocco
- Laboratory of Health Sciences and Technologies, Higher Institute of Health Sciences, Hassan First University of Settat, Settat, Morocco
| | - Mounia Oudghiri
- Laboratory of Immunology and Biodiversity, Faculty of Sciences Ain Chock, Hassan II University, Casablanca, Morocco
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23
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Jordan AA, Bhat S, Ali T, Brunskill SR, Clusen NA, Maltz RM, Moise C, Sun X, Thomas HJ, Ray C, Harkins-Schwarz M, Ehrlich OG. Healthcare Access for Patients With Inflammatory Bowel Disease in the United States: A Survey by the Crohn's & Colitis Foundation. Inflamm Bowel Dis 2024:izae237. [PMID: 39377748 DOI: 10.1093/ibd/izae237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Indexed: 10/09/2024]
Abstract
BACKGROUND A prior survey disseminated in 2017 identified that healthcare access barriers exist and significantly affect patients with inflammatory bowel disease (IBD). We sought to identify, through an updated survey, the healthcare access barriers that patients continue to face, with a focus on socioeconomic factors and patient awareness of resources to navigate existing barriers. METHODS A 52-question online survey evaluating (1) access to healthcare professionals, medications, and procedures; (2) associated financial challenges; and (3) patient awareness of education and advocacy tools to navigate IBD care barriers, was disseminated through multiple channels to IBD patients and their caregivers. RESULTS Of the 2281 completed responses, patients on advanced specialty medications, younger than 65 years of age, or on employer insurance experienced significantly greater issues with insurance barriers to accessing medications and coverage of medically necessary tests/treatments. Patients who live in areas of concentrated poverty were more likely to experience poor health outcomes when subjected to step therapy compared to patients who did not. Additionally, patients were more likely to experience one or more financial barriers or trade-offs if the patient used an advanced specialty medicine or lived in an area with concentrated poverty. CONCLUSIONS While there have been significant and numerous advancements in IBD treatments, patients with IBD continue to experience barriers to healthcare access and treatment and financial struggles. Ongoing awareness and advocacy efforts focused on healthcare system reform and related policies to further minimize care disparities and barriers remain vital.
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Affiliation(s)
- Ariel A Jordan
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Shubha Bhat
- Department of Pharmacy, Cleveland Clinic Foundation, Cleveland, OH, USA
- Department of Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Tauseef Ali
- Crohn's and Colitis Center, SSM Health St. Anthony Hospital Digestive Care, Oklahoma City, OK, USA
| | | | | | - Ross M Maltz
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children's Hospital, Columbus, OH, USA
- Department of Pediatrics, The Ohio State Wexner Medical Center, Columbus, OH, USA
| | | | | | | | - Cassie Ray
- Crohn's & Colitis Foundation, New York, NY, USA
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24
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Neupane YR, Yogananda TM, Rompicharla SVK, Selaru FM, Ensign LM. Emerging therapeutics for the management of intestinal fibrosis and strictures. ADVANCES IN PHARMACOLOGY (SAN DIEGO, CALIF.) 2024; 101:107-139. [PMID: 39521597 DOI: 10.1016/bs.apha.2024.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Chronic intestinal inflammation in patients with inflammatory bowel disease (IBD) can lead to the development of fibrosis and the formation of strictures. Endoscopic balloon dilation and surgical resection are currently the only available treatments for fibrotic strictures. However, both strategies are associated with potential complications and high rates of stricture recurrence, necessitating additional procedures and/or multiple surgical resections. IBD therapeutic modalities aimed at inflammation, including anti-inflammatory agents, such as corticosteroids, biologics and small molecules, have shown limited efficacy in altering the natural history of strictures, ameliorating fibrosis progression, or preventing recurrences. New and innovative therapeutic approaches targeted at fibrosis are urgently needed. Herein, we provide an overview of emerging therapeutics, including novel drug delivery systems, for the management of intestinal fibrosis and strictures.
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Affiliation(s)
- Yub Raj Neupane
- Center for Nanomedicine at the Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Thanuja Marasarakottige Yogananda
- Center for Nanomedicine at the Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Sri Vishnu Kiran Rompicharla
- Center for Nanomedicine at the Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Florin M Selaru
- Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Oncology, Sidney Kimmel Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; The Institute for Nanobiotechnology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Laura M Ensign
- Center for Nanomedicine at the Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Oncology, Sidney Kimmel Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Departments of Gynecology and Obstetrics, Pharmacology and Molecular Sciences, and Medicine (Infectious Diseases), The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
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Krugliak Cleveland N, Candela N, Carter JA, Kuharic M, Qian J, Tang Z, Turpin R, Rubin DT. Real-World Treatment Outcomes Associated With Early Versus Delayed Vedolizumab Initiation in Patients With Ulcerative Colitis. CROHN'S & COLITIS 360 2024; 6:otae061. [PMID: 39502268 PMCID: PMC11535256 DOI: 10.1093/crocol/otae061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Indexed: 11/08/2024] Open
Abstract
Background Patients with ulcerative colitis (UC) typically receive a targeted inflammatory bowel disease therapy after treatment with conventional therapies and after the development of significant morbidity. Evidence suggests that early biologic treatment after diagnosis could improve treatment response and prevent disease complications compared with delayed biologic treatment after conventional therapy. Methods RALEE was a retrospective study using claims data from IBM® MarketScan® Research Databases between January 1, 2016 and December 31, 2019. Adults with UC and at least one claim for vedolizumab were categorized into Early or Delayed Vedolizumab groups according to whether they had received vedolizumab within 30 days of diagnosis or after conventional therapy (5-aminosalicylates, corticosteroids, and immunomodulators), respectively. Treatment response was assessed at 2, 6, and 12 months after vedolizumab treatment initiation and was analyzed with logistic regression (bivariate). Results At 2 months, Delayed Vedolizumab was associated with significantly higher odds of nonresponse than Early Vedolizumab (odds ratio [OR], 2.509; 95% confidence interval [CI], 1.28-4.90). Delayed Vedolizumab was not significantly associated with odds of nonresponse at 6 months (OR, 1.173; 95% CI, 0.72-1.90) or at 12 months (OR, 0.872; 95% CI, 0.55-1.37). Mean total healthcare costs were similar in the Early Vedolizumab ($6492) and Delayed Vedolizumab ($5897) groups, although there were small differences in costs from different types of claims. Conclusions Patients who received vedolizumab early after UC diagnosis were less likely to experience nonresponse at 2 months and incurred similar healthcare costs at 12 months compared with patients who received delayed vedolizumab.
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Affiliation(s)
| | - Ninfa Candela
- Takeda Pharmaceuticals USA, Inc., Lexington, MA, USA
| | | | - Maja Kuharic
- Department of Pharmacy Systems, Outcomes and Policy, University of Illinois Chicago, Chicago, IL, USA
| | | | | | - Robin Turpin
- Takeda Pharmaceuticals USA, Inc., Lexington, MA, USA
| | - David T Rubin
- University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, IL, USA
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Young D, Harris C, Rahmany S, Iria I, Gonçalves J, Addison J, Harvey J, Latter S, Cummings F. A randomised, crossover trial exploring the patient perspective and effectiveness of biosimilar adalimumab transition: IBD reference and biosimilar adalimumab cross over study (iBaSS). Int J Clin Pharm 2024; 46:1091-1101. [PMID: 38734866 DOI: 10.1007/s11096-024-01739-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 04/05/2024] [Indexed: 05/13/2024]
Abstract
BACKGROUND Patient satisfaction has been positively associated with adherence which is expected to impact outcomes. Although vital for successful implementation of biosimilar medicines, little is known about the patient perspective of transition. AIM The aim of this study was to investigate clinical outcomes and patient experience of transitioning between reference adalimumab and a biosimilar (SB5). METHOD iBaSS is a phase IV single-centre, prospective, randomised, single-blind, cross-over study in adult subjects with Crohn's disease. Participants, stable on adalimumab before consent, received 24 weeks of treatment with both reference adalimumab and SB5. The primary outcome was the proportion of patients maintaining baseline clinical status throughout each treatment period, with patients' perspective of disease control and treatment satisfaction assessed as secondary outcomes. RESULTS A total of 112 participants, representative of the heterogeneous patient populations encountered in routine clinical practice, were enrolled. A similar proportion of participants maintained baseline clinical status through each treatment period: 81.8% with reference adalimumab and 79.5% with SB5. Patient reported outcomes (IBD-Control questionnaire (SB5: 15.5; reference adalimumab 15) and TSQM), adverse events and therapeutic drug monitoring remained consistent through both treatment periods, although a higher median injection pain VAS score was noted with SB5 (53/100 versus 6/100 with reference adalimumab). The number of switches undertaken in the study did not impact serum drug concentration or immunogenicity. CONCLUSION This study, mimicking real world adalimumab transition, demonstrates that patients undertaking brand transition can be expected to have consistent clinical and satisfaction outcomes. CLINICAL TRIAL REGISTERED WITH EUDRACT Number 2018-004967-30.
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Affiliation(s)
- David Young
- Pharmacy Department, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK.
- Faculty of Medicine, University of Southampton, Southampton, UK.
| | - Clare Harris
- Faculty of Medicine, University of Southampton, Southampton, UK
- Department of Gastroenterology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Sohail Rahmany
- Department of Gastroenterology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Inês Iria
- Faculdade de Farmacia, Universidade Lisboa, Lisbon, Portugal
| | - João Gonçalves
- Faculdade de Farmacia, Universidade Lisboa, Lisbon, Portugal
| | | | - Justin Harvey
- Department of Statistics and Actuarial Science, Stellenbosch University, Stellenbosch, South Africa
| | - Sue Latter
- School of Health Sciences, University of Southampton, Southampton, UK
| | - Fraser Cummings
- Faculty of Medicine, University of Southampton, Southampton, UK
- Department of Gastroenterology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
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Shah S, Shillington AC, Kabagambe EK, Deering KL, Babin S, Capelouto J, Pulliam C, Patel A, LaChappelle B, Liu J. Racial and Ethnic Disparities in Patients With Inflammatory Bowel Disease: An Online Survey. Inflamm Bowel Dis 2024; 30:1467-1474. [PMID: 37703380 PMCID: PMC11369073 DOI: 10.1093/ibd/izad194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Indexed: 09/15/2023]
Abstract
BACKGROUND Data regarding care access and outcomes in Black/Indigenous/People of Color/Hispanic (BIPOC/H) individuals is limited. This study evaluated care barriers, disease status, and outcomes among a diverse population of White/non-Hispanic (W/NH) and BIPOC/H inflammatory bowel disease (IBD) patients at a large U.S. health system. METHODS An anonymous online survey was administered to adult IBD patients at Ochsner Health treated between Aug 2019 and Dec 2021. Collected data included symptoms, the Consumer Assessment of Healthcare Providers and Systems and Barriers to Care surveys, health-related quality of life (HRQOL) via the Short Inflammatory Bowel Disease Questionnaire, the Medication Adherence Rating Scale-4, and the Beliefs about Medicines Questionnaire. Medical record data examined healthcare resource utilization. Analyses compared W/NH and BIPOC/H via chi-square and t tests. RESULTS Compared with their W/NH counterparts, BIPOC/H patients reported more difficulties accessing IBD specialists (26% vs 11%; P = .03), poor symptom control (35% vs 18%; P = .02), lower mean HRQOL (41 ± 14 vs 49 ± 13; P < .001), more negative impact on employment (50% vs 33%; P = .029), worse financial stability (53% vs 32%; P = .006), and more problems finding social/emotional support for IBD (64% vs 37%; P < .001). BIPOC/H patients utilized emergency department services more often (42% vs 22%; P = .004), reported higher concern scores related to IBD medication (17.1 vs 14.9; P = .001), and worried more about medication harm (19.5% vs 17.7%; P = .002). The survey response rate was 14%. CONCLUSIONS BIPOC/H patients with IBD had worse clinical disease, lower HRQOL scores, had more medication concerns, had less access to specialists, had less social and emotional support, and used emergency department services more often than W/NH patients.
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Affiliation(s)
- Shamita Shah
- Department of Gastroenterology, Ochsner Health, New Orleans, LA, USA
| | | | - Edmond Kato Kabagambe
- Department of Gastroenterology, Ochsner Health, New Orleans, LA, USA
- Research Administration, Penn Medicine Lancaster General Health, Lancaster, PA, USA
| | | | - Sheena Babin
- Department of Gastroenterology, Ochsner Health, New Orleans, LA, USA
| | - Joseph Capelouto
- Department of Gastroenterology, Ochsner Health, New Orleans, LA, USA
| | | | - Aarti Patel
- Population Health, Janssen Scientific Affairs, LLC, Titusville, NJ, USA
| | | | - Julia Liu
- Department of Gastroenterology, Morehouse School of Medicine, Atlanta, GA, USA
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Privitera G, Bezzio C, Dal Buono A, Gabbiadini R, Loy L, Brandaleone L, Marcozzi G, Migliorisi G, Armuzzi A. How comparative studies can inform treatment decisions for Crohn's disease. Expert Opin Biol Ther 2024; 24:955-972. [PMID: 39132872 DOI: 10.1080/14712598.2024.2389985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 08/05/2024] [Indexed: 08/13/2024]
Abstract
INTRODUCTION As new therapies for the treatment of Crohn's disease (CD) are approved, there is an increasing need for evidence that clarifies their positioning and sequencing. AREAS COVERED Comparative effectiveness research (CER) aims to inform physicians' decisions when they choose which intervention (drug or treatment strategy) to administer to their patients. Pragmatic head-to-head trials represent the best tools for CER, but only a few have been published in the IBD field. Network meta-analyses can point toward the superiority of one drug over another, but they do not reflect everyday clinical practice. Finally, real-world evidence complements that coming from head-to-head trials and network meta-analyses, assessing the real-life effectiveness of therapeutic interventions. EXPERT OPINION There is insufficient evidence to create a definitive therapeutic algorithm for CD, but some general considerations can be made. Anti-TNF-α agents seemingly represent the most 'sustainable' first-line choice, considering benefit-harm ratio and costs; vedolizumab, ustekinumab, and risankizumab may be considered as first-line choice when safety issues become prominent. In the event of pharmacodynamic failure, out-of-class swap is to be preferred - possibly with anti-IL23p19 as the best option, with unclear data regarding upadacitinib positioning; a second anti-TNF-α could be considered, as a second choice, after pharmacokinetic failure.
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Affiliation(s)
- Giuseppe Privitera
- Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy
| | - Cristina Bezzio
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Arianna Dal Buono
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | | | - Laura Loy
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Luca Brandaleone
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Giacomo Marcozzi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Giulia Migliorisi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Alessandro Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
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Keever-Keigher MR, Harvey L, Williams V, Vyhlidal CA, Ahmed AA, Johnston JJ, Louiselle DA, Grundberg E, Pastinen T, Friesen CA, Chevalier R, Smail C, Shakhnovich V. Genomic insights into pediatric intestinal inflammatory and eosinophilic disorders using single-cell RNA-sequencing. Front Immunol 2024; 15:1420208. [PMID: 39192974 PMCID: PMC11347318 DOI: 10.3389/fimmu.2024.1420208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 07/26/2024] [Indexed: 08/29/2024] Open
Abstract
Introduction Chronic inflammation of the gastrointestinal tissues underlies gastrointestinal inflammatory disorders, leading to tissue damage and a constellation of painful and debilitating symptoms. These disorders include inflammatory bowel diseases (Crohn's disease and ulcerative colitis), and eosinophilic disorders (eosinophilic esophagitis and eosinophilic duodenitis). Gastrointestinal inflammatory disorders can often present with overlapping symptoms necessitating the use of invasive procedures to give an accurate diagnosis. Methods This study used peripheral blood mononuclear cells from individuals with Crohn's disease, ulcerative colitis, eosinophilic esophagitis, and eosinophilic duodenitis to better understand the alterations to the transcriptome of individuals with these diseases and identify potential markers of active inflammation within the peripheral blood of patients that may be useful in diagnosis. Single-cell RNA-sequencing was performed on peripheral blood mononuclear cells isolated from the blood samples of pediatric patients diagnosed with gastrointestinal disorders, including Crohn's disease, ulcerative colitis, eosinophilic esophagitis, eosinophilic duodenitis, and controls with histologically healthy gastrointestinal tracts. Results We identified 730 (FDR < 0.05) differentially expressed genes between individuals with gastrointestinal disorders and controls across eight immune cell types. Discussion There were common patterns among GI disorders, such as the widespread upregulation of MTRNR2L8 across cell types, and many differentially expressed genes showed distinct patterns of dysregulation among the different gastrointestinal diseases compared to controls, including upregulation of XIST across cell types among individuals with ulcerative colitis and upregulation of Th2-associated genes in eosinophilic disorders. These findings indicate both overlapping and distinct alterations to the transcriptome of individuals with gastrointestinal disorders compared to controls, which provide insight as to which genes may be useful as markers for disease in the peripheral blood of patients.
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Affiliation(s)
| | - Lisa Harvey
- Children’s Mercy Kansas City, Kansas, MO, United States
| | | | | | - Atif A. Ahmed
- Seattle Children’s Hospitals, University of Washington, Seattle, WA, United States
| | | | | | - Elin Grundberg
- Children’s Mercy Kansas City, Kansas, MO, United States
- School of Medicine, University of Missouri-Kansas City, Kansas, MO, United States
| | - Tomi Pastinen
- Children’s Mercy Kansas City, Kansas, MO, United States
- School of Medicine, University of Missouri-Kansas City, Kansas, MO, United States
| | - Craig A. Friesen
- Children’s Mercy Kansas City, Kansas, MO, United States
- School of Medicine, University of Missouri-Kansas City, Kansas, MO, United States
| | - Rachel Chevalier
- Children’s Mercy Kansas City, Kansas, MO, United States
- School of Medicine, University of Missouri-Kansas City, Kansas, MO, United States
| | - Craig Smail
- Children’s Mercy Kansas City, Kansas, MO, United States
- School of Medicine, University of Missouri-Kansas City, Kansas, MO, United States
| | - Valentina Shakhnovich
- Children’s Mercy Kansas City, Kansas, MO, United States
- School of Medicine, University of Missouri-Kansas City, Kansas, MO, United States
- Ironwood Pharmaceuticals, Boston, MA, United States
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30
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Mestrovic A, Perkovic N, Bozic D, Kumric M, Vilovic M, Bozic J. Precision Medicine in Inflammatory Bowel Disease: A Spotlight on Emerging Molecular Biomarkers. Biomedicines 2024; 12:1520. [PMID: 39062093 PMCID: PMC11274502 DOI: 10.3390/biomedicines12071520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/30/2024] [Accepted: 07/06/2024] [Indexed: 07/28/2024] Open
Abstract
Inflammatory bowel diseases (IBD) remain challenging in terms of understanding their causes and in terms of diagnosing, treating, and monitoring patients. Modern diagnosis combines biomarkers, imaging, and endoscopic methods. Common biomarkers like CRP and fecal calprotectin, while invaluable tools, have limitations and are not entirely specific to IBD. The limitations of existing markers and the invasiveness of endoscopic procedures highlight the need to discover and implement new markers. With an ideal biomarker, we could predict the risk of disease development, as well as the possibility of response to a particular therapy, which would be significant in elucidating the pathogenesis of the disease. Recent research in the fields of machine learning, proteomics, epigenetics, and gut microbiota provides further insight into the pathogenesis of the disease and is also revealing new biomarkers. New markers, such as BAFF, PGE-MUM, oncostatin M, microRNA panels, αvβ6 antibody, and S100A12 from stool, are increasingly being identified, with αvβ6 antibody and oncostatin M being potentially close to being presented into clinical practice. However, the specificity of certain markers still remains problematic. Furthermore, the use of expensive and less accessible technology for detecting new markers, such as microRNAs, represents a limitation for widespread use in clinical practice. Nevertheless, the need for non-invasive, comprehensive markers is becoming increasingly important regarding the complexity of treatment and overall management of IBD.
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Affiliation(s)
- Antonio Mestrovic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Nikola Perkovic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Dorotea Bozic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Marko Kumric
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Marino Vilovic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
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Law CCY, Tkachuk B, Lieto S, Narula N, Walsh S, Colombel JF, Ungaro RC. Early Biologic Treatment Decreases Risk of Surgery in Crohn's Disease but not in Ulcerative Colitis: Systematic Review and Meta-Analysis. Inflamm Bowel Dis 2024; 30:1080-1086. [PMID: 37506265 PMCID: PMC11219475 DOI: 10.1093/ibd/izad149] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Indexed: 07/30/2023]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease (IBD) can lead to long-term complications that significantly impact patients' quality of life and healthcare resource utilization. Prior studies have demonstrated improved short-term outcomes to early exposure of biologics in patients with Crohn's disease (CD) but not in patients with ulcerative colitis (UC). However, there are conflicting data on impact of early intervention on longer-term adverse events. Therefore, we conducted a systematic review and meta-analysis assessing the impact of early biologic treatment on rates of IBD-related surgery. METHODS A systematic search was conducted in April 2022. Studies were included if biologic initiation was compared between patients starting early (<3 years of diagnosis or top-down treatment) vs later (>3 years of diagnosis or step-up treatment). Studies with <1 year of follow-up were excluded. The outcomes were colectomy and CD-related surgery for patients with UC and CD, respectively. Random-effects analyses were conducted to compare rates of IBD surgery between early and late biologic treatment. RESULTS Eighteen studies were included in the meta-analysis. Three studies included patients with UC and 15 studies included patients with CD. In patients with CD, early biologic therapy was associated with lower odds of surgery (odds ratio, 0.63; 95% confidence interval, 0.48-0.84) compared with late treatment. Conversely, in patients with UC, the odds of colectomy were increased (odds ratio, 2.86; 95% confidence interval, 1.30-6.30). CONCLUSIONS Early biologic treatment is associated with lower rates of surgery in patients with CD. In contrast, early biologic therapy appears to be associated with higher rates of colectomy in patients with UC, which may be confounded by disease severity.
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Affiliation(s)
- Cindy C Y Law
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Bryce Tkachuk
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Stephen Lieto
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Neeraj Narula
- Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
| | | | - Jean-Frédéric Colombel
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ryan C Ungaro
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Bhat S, Kane SV. Clinical Guide to Navigating the Landscape of Biosimilars for Inflammatory Bowel Disease. Gastroenterol Hepatol (N Y) 2024; 20:376-382. [PMID: 39206027 PMCID: PMC11348546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Annual out-of-pocket expenditures for patients with inflammatory bowel disease (IBD) are estimated to be as high as $41,000, with medications, such as biologics, being one of the main cost contributors. Although biologics have revolutionized IBD management, these medications are costly owing to their molecular makeup and manufacturing processes. Biosimilars, which are biologic medications that are highly similar to the US Food and Drug Administration (FDA)-approved reference product with no clinically meaningful differences in safety, purity, or potency, offer the same therapeutic benefits at a reduced cost. Other additional benefits offered with biosimilars include increased treatment access and fostered development of new therapeutic options. Despite the expansion of biosimilars in IBD, their adoption and utilization have been suboptimal in the United States. This article provides an overview of the biosimilar landscape in IBD, including FDA-approved biosimilars available, and a clinical guide to navigate switching to biosimilars in various clinical scenarios based on current evidence.
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Affiliation(s)
- Shubha Bhat
- Digestive Disease and Surgery Institute and Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio
| | - Sunanda V. Kane
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Larsen L, Olesen AE, Nayeb AB, Grøntved S, Krarup AL. Beyond diagnosis: investigating hospital referral impact on biological treatment initiation, hospital admission, and surgery patterns in inflammatory bowel disease - a Danish population based study. Scand J Gastroenterol 2024; 59:690-697. [PMID: 38567864 DOI: 10.1080/00365521.2024.2337829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 03/21/2024] [Accepted: 03/27/2024] [Indexed: 05/30/2024]
Abstract
OBJECTIVES Early biological treatment in patients with inflammatory bowel disease (IBD) is important in disease control. Previous studies have suggested that patients with IBD from Non-Academic Hospitals were less likely to receive biologics. The aims of this study were (1) to use the granular data in the clinical database, GASTROBIO, to study detailed differences in time from IBD diagnosis to first administration of biologics, hospital admission, and surgery in patients referred to Academic Hospitals versus to Non-Academic Hospitals, and (2) to explore differences in disease extent, behavior, and indication for biological treatment. MATERIAL AND METHODS This was a retrospective cross-sectional descriptive population-based quality study of patients with IBD initiating biologics in the North Denmark Region between 2016 and 2018. Data from GASTROBIO were extracted, namely demographic data, time of diagnosis, biological treatments with indications, hospital admission, and surgery. RESULTS Of the 146 patients included, 84 were from the Academic and 62 from the Non-Academic Hospitals. No significant differences in median time from diagnosis to (1) treatment, (2) hospital admission or (3) IBD surgery between the groups were observed. A higher percentage of patients with luminal Crohn's disease were treated with biologics at the Academic Hospital (78% and 66%). CONCLUSIONS Based on the findings of this population-based study, we found no evidence that the referral area had a significant impact on the duration from diagnosis to the initiation of biological treatment, hospital admissions, or surgery. However, the data suggested that fewer patients with luminal Crohn's disease were referred to biologics from Non-Academic Hospitals.
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Affiliation(s)
- Lone Larsen
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Department of Clinical Medicine, The Faculty of Medicine, Aalborg University, Aalborg, Denmark
| | - Anne Estrup Olesen
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Clinical Pharmacology, Aalborg University Hospital, Aalborg, Denmark
| | - Alev Büyükuslu Nayeb
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Simon Grøntved
- Region North Psychiatry, Aalborg University Hospital, Aalborg, Denmark
- Danish Center for Health Services Research, Aalborg University, Aalborg, Denmark
| | - Anne Lund Krarup
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Emergency Medicine and Trauma Center, Aalborg University Hospital, Aalborg, Denmark
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Jayasooriya N, Saxena S, Blackwell J, Bottle A, Creese H, Petersen I, Pollok RCG. Associations between prior healthcare use, time to diagnosis, and clinical outcomes in inflammatory bowel disease: a nationally representative population-based cohort study. BMJ Open Gastroenterol 2024; 11:e001371. [PMID: 38802264 PMCID: PMC11131120 DOI: 10.1136/bmjgast-2024-001371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 04/23/2024] [Indexed: 05/29/2024] Open
Abstract
BACKGROUND Timely diagnosis and treatment of inflammatory bowel disease (IBD) may improve clinical outcomes. OBJECTIVE Examine associations between time to diagnosis, patterns of prior healthcare use, and clinical outcomes in IBD. DESIGN Using the Clinical Practice Research Datalink we identified incident cases of Crohn's disease (CD) and ulcerative colitis (UC), diagnosed between January 2003 and May 2016, with a first primary care gastrointestinal consultation during the 3-year period prior to IBD diagnosis. We used multivariable Cox regression to examine the association of primary care consultation frequency (n=1, 2, >2), annual consultation intensity, hospitalisations for gastrointestinal symptoms, and time to diagnosis with a range of key clinical outcomes following diagnosis. RESULTS We identified 2645 incident IBD cases (CD: 782; UC: 1863). For CD, >2 consultations were associated with intestinal surgery (adjusted HR (aHR)=2.22, 95% CI 1.45 to 3.39) and subsequent CD-related hospitalisation (aHR=1.80, 95% CI 1.29 to 2.50). For UC, >2 consultations were associated with corticosteroid dependency (aHR=1.76, 95% CI 1.28 to 2.41), immunomodulator use (aHR=1.68, 95% CI 1.24 to 2.26), UC-related hospitalisation (aHR=1.43, 95% CI 1.05 to 1.95) and colectomy (aHR=2.01, 95% CI 1.22 to 3.27). For CD, hospitalisation prior to diagnosis was associated with CD-related hospitalisation (aHR=1.30, 95% CI 1.01 to 1.68) and intestinal surgery (aHR=1.71, 95% CI 1.13 to 2.58); for UC, it was associated with immunomodulator use (aHR=1.42, 95% CI 1.11 to 1.81), UC-related hospitalisation (aHR=1.36, 95% CI 1.06 to 1.95) and colectomy (aHR=1.54, 95% CI 1.01 to 2.34). For CD, consultation intensity in the year before diagnosis was associated with CD-related hospitalisation (aHR=1.19, 95% CI 1.12 to 1.28) and intestinal surgery (aHR=1.13, 95% CI 1.03 to 1.23); for UC, it was associated with corticosteroid use (aHR=1.08, 95% CI 1.04 to 1.13), corticosteroid dependency (aHR=1.05, 95% CI 1.00 to 1.11), and UC-related hospitalisation (aHR=1.12, 95% CI 1.03 to 1.21). For CD, time to diagnosis was associated with risk of CD-related hospitalisation (aHR=1.03, 95% CI 1.01 to 1.68); for UC, it was associated with reduced risk of UC-related hospitalisation (aHR=0.83, 95% CI 0.70 to 0.98) and colectomy (aHR=0.59, 95% CI 0.43 to 0.80). CONCLUSION Electronic records contain valuable information about patterns of healthcare use that can be used to expedite timely diagnosis and identify aggressive forms of IBD.
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Affiliation(s)
- Nishani Jayasooriya
- Institute for Infection and Immunity, St George's University of London, London, UK
- Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK
| | - Sonia Saxena
- Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK
| | - Jonathan Blackwell
- Edinburgh Inflammatory Bowel Disease, Western General Hospital, Edinburgh, UK
| | - Alex Bottle
- Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK
| | - Hanna Creese
- Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK
| | - Irene Petersen
- Research Department of Primary Care and Population Health, University College London, London, UK
| | - Richard C G Pollok
- Institute for Infection and Immunity, St George's University of London, London, UK
- Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
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Hawthorne AB, Arms-Williams B, Cannings-John R, Pollok RCG, Berry A, Harborne P, Trivedi A. Impact of antitumour necrosis factor therapy on surgery in inflammatory bowel disease: a population-based study. BMJ Open Gastroenterol 2024; 11:e001373. [PMID: 38777566 PMCID: PMC11116861 DOI: 10.1136/bmjgast-2024-001373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 05/02/2024] [Indexed: 05/25/2024] Open
Abstract
OBJECTIVE It is unclear whether widespread use of biologics is reducing inflammatory bowel disease (IBD) surgical resection rates. We designed a population-based study evaluating the impact of early antitumour necrosis factor (TNF) on surgical resection rates up to 5 years from diagnosis. DESIGN We evaluated all patients with IBD diagnosed in Cardiff, Wales 2005-2016. The primary measure was the impact of early (within 1 year of diagnosis) sustained (at least 3 months) anti-TNF compared with no therapy on surgical resection rates. Baseline factors were used to balance groups by propensity scores, with inverse probability of treatment weighting (IPTW) methodology and removing immortal time bias. Crohn's disease (CD) and ulcerative colitis (UC) with IBD unclassified (IBD-U) (excluding those with proctitis) were analysed. RESULTS 1250 patients were studied. For CD, early sustained anti-TNF therapy was associated with a reduced likelihood of resection compared with no treatment (IPTW HR 0.29 (95% CI 0.13 to 0.65), p=0.003). In UC including IBD-U (excluding proctitis), there was an increase in the risk of colectomy for the early sustained anti-TNF group compared with no treatment (IPTW HR 4.6 (95% CI 1.9 to 10), p=0.001). CONCLUSIONS Early sustained use of anti-TNF therapy is associated with reduced surgical resection rates in CD, but not in UC where there was a paradoxical increased surgery rate. This was because baseline clinical factors were less predictive of colectomy than anti-TNF usage. These data support the use of early introduction of anti-TNF therapy in CD whereas benefit in UC cannot be assessed by this methodology.
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Affiliation(s)
- A Barney Hawthorne
- Department of Gastroenterology, Cardiff and Vale University Health Board, Cardiff, UK
- Biomedical Sciences, Cardiff University, Cardiff, UK
| | - Bradley Arms-Williams
- Department of Gastroenterology, Cardiff and Vale University Health Board, Cardiff, UK
| | - Rebecca Cannings-John
- Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University, Cardiff, UK
| | - Richard C G Pollok
- Dept Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
- Institute for Infection and Immunity, St George's University, London, UK
| | - Alexander Berry
- Department of Gastroenterology, Cardiff and Vale University Health Board, Cardiff, UK
| | - Philip Harborne
- Department of Gastroenterology, Cardiff and Vale University Health Board, Cardiff, UK
| | - Anjali Trivedi
- Department of Gastroenterology, Cardiff and Vale University Health Board, Cardiff, UK
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Tran P, Tjahja M, Wang Y, Seth N, Reyes R, Bussell C, Edwards A, Johnson CM. Close outpatient follow-up associated with reduced readmission rates in patients with inflammatory bowel disease. Proc AMIA Symp 2024; 37:517-524. [PMID: 38910831 PMCID: PMC11188799 DOI: 10.1080/08998280.2024.2335095] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 03/18/2024] [Indexed: 06/25/2024] Open
Abstract
Background Few studies have shown the effects of prompt outpatient follow-up in relation to reducing readmission rates in patients hospitalized with inflammatory bowel disease (IBD). Our study evaluated whether postdischarge follow-up was associated with fewer IBD-related readmissions. Methods This single-center retrospective study included 477 patients with Crohn's disease (CD) or ulcerative colitis (UC) who were readmitted to our tertiary care hospital from January 1, 2016, to June 1, 2022. Rehospitalization admissions were defined as admissions that occurred within 90 days after discharge date. We used a chi-square or Fisher's exact test to test for bivariate comparisons to determine if there was an association in patients readmitted for IBD and primary care or gastroenterology follow-up at 1, 2, 3, and 4 weeks versus no follow-up. Results In UC patients, there were 118 admissions from 2016 to 2022; 36/118 (31%) and 41/118 (34.7%) of the patients were readmitted at 30 days and 90 days, respectively. In the CD group, there were 101 (36.73%) readmissions among 277 patients, with 174 nonreadmissions (63.27%). Conclusions Gastroenterology follow-up within 1 month was associated with reduced rates of admission in both groups (P < 0.05). This study highlights the importance of close gastroenterology follow-up for IBD-related hospitalizations.
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Affiliation(s)
- Phi Tran
- Department of Internal Medicine, Baylor Scott and White Medical Center, Temple, Texas, USA
| | - Matthew Tjahja
- Department of Internal Medicine, Baylor Scott and White Medical Center, Temple, Texas, USA
| | - Yilun Wang
- Texas A&M School of Medicine, College Station, Bryan, Texas, USA
| | - Nikhil Seth
- Department of Internal Medicine, Baylor Scott and White Medical Center, Temple, Texas, USA
| | - Rylyn Reyes
- Division of Gastroenterology, Baylor Scott and White Medical Center, Temple, Texas, USA
| | - Charles Bussell
- Division of Gastroenterology, Baylor Scott and White Medical Center, Temple, Texas, USA
| | - Audrene Edwards
- Baylor Scott and White Research Institute, Dallas, Texas, USA
| | - Christopher M. Johnson
- Department of Internal Medicine, Baylor Scott and White Medical Center, Temple, Texas, USA
- Division of Gastroenterology, Baylor Scott and White Medical Center, Temple, Texas, USA
- Baylor College of Medicine, Temple, Texas, USA
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Alavinejad P, Hashemi SJ, Behl N, Hormati A, Elbasuny A, Daryani NE, Modarres MP, Arshadzadeh M, Panahande S, Hang DV, Mahros AM, Parsi A, Javaherizadeh H, Rehman A, Pawlak KM, Ahmadi M, Ahmed MH, Farsi F, Arefi M, Quadri A, Tran QT, Alborzi F, Amin Alavi SM, Cheraghian B, Ramezani E, Gouda MF, Saadati B, Quadri AA, Hirani R, Maher M, Ghoneem E. Inflammatory bowel disease evolution in the past two decades: a chronological multinational study. EClinicalMedicine 2024; 70:102542. [PMID: 38525407 PMCID: PMC10959644 DOI: 10.1016/j.eclinm.2024.102542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 02/20/2024] [Accepted: 02/27/2024] [Indexed: 03/26/2024] Open
Abstract
Background The multifactorial nature of inflammatory bowel disease (IBD), which manifests differently in individuals creates a need for a better understanding of the behaviour and pattern of the disease due to environmental factors. The current study aimed to study the changes in IBD behaviour, presentation, and characteristics in patients over the past two decades with a goal of improving patients' diagnosis, management and outcomes. Methods During a 6-month period (1/02/2022-30/07/2022), the information of patients with IBD who attended IBD outpatient clinics of 11 referral centre's in six countries was collected, and based on the first time of diagnosis with IBD, they were allocated as group A (those who were diagnosed more than 15 years ago), group B (those who were diagnosed with IBD between 5 and 15 years ago) and group C (IBD cases who diagnosed in recent 5 years). Then the most prevalent subtypes and characters of the disease are evaluated and compared to make clear if the presenting pattern and behaviour of the disease has changed in the last 2 decades. Findings Overall 1430 patients with IBD including 1207 patients with ulcerative colitis (UC) (84.5%) and 205 patients with Crohn's disease (CD; 14.3%) included. Mean age of participants at the first time of diagnosis with IBD was 30 years. The extra-intestinal involvement of IBD in groups A and B was more prevalent in comparison with group C. Most of those in groups A & B had academic education but in group C, the most prevalent educational status was high school or diploma (P = 0.012). In contrast to groups A and B, the relative prevalence of medium socioeconomic level in group C had decreased (65%). Relative prevalence of UC subtypes was similar among groups A and B (extensive colitis as most prevalent) but in group C, the most prevalent subtype is left side colitis (38.17%). The most prevalent subtype of CD in groups A and B was ileocolic involvement while in group C, upper GI involvement is significantly increased. The rate of food sensitivity among groups A and B was more than group C (P = 0.00001). The relative prevalence of patients with no flare has increased with a steady slope (P < 0.00001). Relative prevalence of presenting symptoms among patients with UC in group C differs and nowadays the rate abdominal pain (70.7%) and bloating (43.9%) have increased and frequency of diarrhoea (67.4%) has decreased. Interpretation In the recent 5 years, the pattern of UC presentation has changed. The rate of upper GI involvement in CD and relative prevalence of patients with no disease flare increased and the rate of extra intestinal involvement decreased. Funding None.
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Affiliation(s)
- Pezhman Alavinejad
- Alimentary Tract Research Centre, Imam Khomeini Hospital Clinical Research Development Unit, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyed Jalal Hashemi
- Alimentary Tract Research Centre, Imam Khomeini Hospital Clinical Research Development Unit, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Nitin Behl
- Institute of Gastro and Liver Diseases, Fortis Hospital, Ludhiana, India
| | - Ahmad Hormati
- Liver and Pancreatobiliary Diseases Research Centre, Digestive Diseases Research Institute, Shariati Hospital, Department of Internal Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Abubakr Elbasuny
- Mit Ghamr Oncology Centre, Gastroenterology and Hepatology Department, Faculty of Medicine, Mansoura University, Egypt
| | | | | | - Masoud Arshadzadeh
- Imam Khomeini Hospital GI Ward, Tehran University of Medical Sciences, Tehran, Iran
| | - Samira Panahande
- Alimentary Tract Research Centre, Imam Khomeini Hospital Clinical Research Development Unit, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Dao Viet Hang
- Internal Medicine Faculty, Hanoi Medical University, Endoscopy Centre, Hanoi Medical University Hospital, Hanoi, Vietnam
| | - Aya Mohammed Mahros
- Hepatology, Gastroenterology and Infectious Diseases, Kafrelsheikh University, Kafrelsheikh, Egypt
| | - Abazar Parsi
- Alimentary Tract Research Centre, Imam Khomeini Hospital Clinical Research Development Unit, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hazhir Javaherizadeh
- Alimentary Tract Research Centre, Imam Khomeini Hospital Clinical Research Development Unit, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ata Rehman
- Faisalabad Medical University, Faisalabad, Pakistan
| | - Katarzyna M. Pawlak
- Division of Gastroenterology Department, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | - Mitra Ahmadi
- Alimentary Tract Research Centre, Imam Khomeini Hospital Clinical Research Development Unit, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammed Hussien Ahmed
- Hepatology, Gastroenterology and Infectious Diseases, Kafrelsheikh University, Kafrelsheikh, Egypt
| | - Farnaz Farsi
- Minimally Invasive Surgery Research Centre, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Arefi
- Toxicology Centre of Baharloo Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Afreen Quadri
- Dr VRK Woman's Medical College, Aziznagar, Telangana, India
| | | | - Foroogh Alborzi
- Imam Khomeini Hospital GI Ward, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Mohammad Amin Alavi
- Alimentary Tract Research Centre, Imam Khomeini Hospital Clinical Research Development Unit, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Bahman Cheraghian
- Alimentary Tract Research Centre, Imam Khomeini Hospital Clinical Research Development Unit, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Elmira Ramezani
- Department of Nutrition, Faculty of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammed Fathi Gouda
- Consultant of Gastroenterology and Endoscopy Theodor Bilharz Research Institute, Giza, Egypt
- Mouwasat Medical Hospital, Dammam, Saudi Arabia
| | | | | | - Rahim Hirani
- School of Medicine, New York Medical College, Valhalla, NY, 10595, USA
| | - Maha Maher
- Gastroenterology and Hepatology (Internal Medicine) Department, Specialised Medical Hospital, Mansoura University
| | - Elsayed Ghoneem
- Mouwasat Medical Hospital, Dammam, Saudi Arabia
- Gastroenterology and Hepatology (Internal Medicine) Department, Specialised Medical Hospital, Mansoura University
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Brun MK, Gehin JE, Bjørlykke KH, Warren DJ, Klaasen RA, Sexton J, Sandanger Ø, Kvien TK, Mørk C, Jahnsen J, Bolstad N, Jørgensen KK, Haavardsholm EA, Goll GL, Syversen SW. Clinical consequences of infliximab immunogenicity and the effect of proactive therapeutic drug monitoring: exploratory analyses of the randomised, controlled NOR-DRUM trials. THE LANCET. RHEUMATOLOGY 2024; 6:e226-e236. [PMID: 38402891 DOI: 10.1016/s2665-9913(23)00341-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 12/15/2023] [Accepted: 12/21/2023] [Indexed: 02/27/2024]
Abstract
BACKGROUND Antidrug antibodies to TNF inhibitors might affect clinical outcomes. Proactive therapeutic drug monitoring allows for early detection of antidrug antibodies and might reduce negative clinical consequences. We aimed to explore how antidrug antibodies to the TNF inhibitor infliximab influence treatment outcomes, and to assess the effect of proactive therapeutic drug monitoring. METHODS This was a predefined exploratory analysis of data from the randomised, controlled NOR-DRUM trials. The trials were conducted in rheumatology, gastroenterology, and dermatology departments at 21 Norwegian hospitals. Adult patients (aged 18-75 years) with immune-mediated inflammatory diseases were randomly assigned to proactive therapeutic drug monitoring or standard infliximab dosing in the NOR-DRUM A trial (30-week follow-up) and the NOR-DRUM B trial (52-week follow-up). Antidrug antibodies were assessed with a drug-sensitive assay before each infusion. The outcomes of remission (at week 30), disease worsening (during 52 weeks), infusion reactions, and infliximab discontinuation were assessed according to the presence of antidrug antibodies and use of therapeutic drug monitoring. FINDINGS Between March 1, 2017, and Dec 12, 2019, 616 patients were included in the NOR-DRUM trials, of whom 615 had at least one serum infliximab and antidrug antibody assessment and were included in the present analyses. Mean age was 45 years (IQR 32-56), 305 (50%) patients were women, and 310 (50%) patients were men. Antidrug antibodies were detected in 147 (24%) patients. Remission at week 30 occurred in 25 (35%) of 72 patients with antidrug antibodies and 180 (54%) of 335 without antidrug antibodies (risk ratio 0·62 [95% CI 0·45-0·86]; p=0·0037). In patients with antidrug antibodies compared with patients without antidrug antibodies, higher rates were found for: disease worsening over 52 weeks (0·76 per person-year vs 0· 35 per person-year, hazard ratio [HR] 2·02 [95% CI 1·33-3·07]; p=0·0009), infusion reactions (0·16 per person-year vs 0·03 per person-year, HR 17·02 [6·98-41·47]; p<0·0001), and infliximab discontinuation (1·00 per person-year vs 0·20 per person-year, HR 6·64 [4·84-9·11]; p<0·0001). These associations were more pronounced in patients with high concentrations of antidrug antibodies than in those with low concentrations of antidrug antibodies. Independent of antibody status, therapeutic drug monitoring was associated with a lower risk of disease worsening (HR 0·41 [0·29-0·59]; p=0·0001) or an infusion reaction (HR 0·30 [0·12-0·73]; p=0·0076), and was associated with an increase in the rate of infliximab discontinuation (HR 1·37 [1·02-1·83]; p=0·037). INTERPRETATION In patients where antidrug antibodies were detected, remission was less likely to be reached and sustained, and infusion reaction or discontinuation of infliximab was more likely. Timely detection of antidrug antibodies by proactive therapeutic drug monitoring facilitated treatment decisions that reduced the negative consequences, both regarding infliximab effectiveness and safety. This highlights the role of proactive therapeutic drug monitoring in optimising infliximab therapy. FUNDING Inter-regional KLINBEFORSK grants and South-Eastern Norway Regional Health Authority grants.
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Affiliation(s)
- Marthe Kirkesæther Brun
- Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - Johanna E Gehin
- Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
| | - Kristin Hammersbøen Bjørlykke
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - David John Warren
- Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
| | - Rolf A Klaasen
- Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
| | - Joseph Sexton
- Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo, Norway
| | | | - Tore K Kvien
- Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Cato Mørk
- Akershus Dermatology Center, Lørenskog, Norway
| | - Jørgen Jahnsen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - Nils Bolstad
- Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
| | | | - Espen A Haavardsholm
- Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Guro Løvik Goll
- Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo, Norway; Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Silje Watterdal Syversen
- Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo, Norway; Institute of Health and Society, University of Oslo, Oslo, Norway
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Bohra A, Connoley DJ, Con D, Segal JP, Niewiadomski O, Vasudevan A, Langenberg DRV, Kutaiba N. Assessing quality of magnetic resonance enterography and its impact on disease assessment of ileal Crohn's disease. Intest Res 2024; 22:152-161. [PMID: 38173229 PMCID: PMC11079513 DOI: 10.5217/ir.2023.00095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 10/01/2023] [Accepted: 11/01/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND/AIMS Assessment of quality of magnetic resonance enterography (MRE) in small bowel Crohn's disease (CD) activity evaluation has received little attention. We assessed the impact of bowel distention and motion artifact on MRE activity indices in ileal CD. METHODS A cohort of patients who underwent contemporaneous MRE and colonoscopy for ileal CD assessment between 2014 and 2021 at 2 centers were audited. An abdominal radiologist blinded to clinical data reviewed each MRE, graded bowel distention and motion artifact upon a pre-specified 3-point scale and calculated the original magnetic resonance index of activity (MaRIA) and simplified MaRIA (sMaRIA), London index and CD MRE index (CDMI). Ileal endoscopic activity was graded via the Simplified Endoscopy Score for CD (SES-CD). The performance of MRE indices in discriminating active disease (SES-CD ≥3) stratified by MRE quality was measured by receiver operator characteristic analyses. RESULTS One hundred and thirty-seven patients had MRE and colonoscopy within a median of 16 days (range, 0-30 days) with 63 (46%) exhibiting active disease (SES-CD ≥3). Forty-four MREs (32%) were deemed low quality due to motion artifact and/or moderate to poor distention. Low-quality MREs demonstrated reduced discriminative performance between ileal SES-CD ≥3 and MRE indices (MaRIA 0.838 vs. 0.634, sMaRIA 0.834 vs. 0.527, CDMI 0.850 vs. 0.595, London 0.748 vs. 0.511, P<0.05 for all). Individually the presence of any motion artifact markedly impacted the discriminative performance (e.g., sMaRIA area under the curve 0.544 vs. 0.814, P<0.05). CONCLUSIONS Image quality parameters can significantly impact MRE disease activity interpretation. Quality metrics should be reported, enabling cautious interpretation in lower-quality studies.
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Affiliation(s)
- Anuj Bohra
- Department of Gastroenterology, Box Hill Hospital, Box Hill, Australia
- Department of Gastroenterology, Northern Hospital, Epping, Australia
- Eastern Health Clinical School, Monash University, Box Hill, Australia
| | - Declan J Connoley
- Department of Gastroenterology, Box Hill Hospital, Box Hill, Australia
| | - Danny Con
- Department of Gastroenterology, Box Hill Hospital, Box Hill, Australia
| | - Jonathan P Segal
- Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, Australia
| | - Olga Niewiadomski
- Department of Gastroenterology, Box Hill Hospital, Box Hill, Australia
| | - Abhinav Vasudevan
- Department of Gastroenterology, Box Hill Hospital, Box Hill, Australia
| | | | - Numan Kutaiba
- Department of Radiology, Box Hill Hospital, Box Hill, Australia
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40
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Lee KE, Tu VY, Faye AS. Optimal Management of Refractory Crohn's Disease: Current Landscape and Future Direction. Clin Exp Gastroenterol 2024; 17:75-86. [PMID: 38558912 PMCID: PMC10981422 DOI: 10.2147/ceg.s359376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 03/22/2024] [Indexed: 04/04/2024] Open
Abstract
Refractory Crohn's disease, defined as ongoing inflammation despite the trial of multiple advanced therapies, impacts a number of individuals with Crohn's disease, and leads to significant burden in quality of life and cost. Interventions such as early implementation of advanced therapies, optimization of current therapies prior to switching to an alternative, as well as understanding the overlapping pathophysiology between immune-mediated disorders, however, can help shift the current landscape and reduce the number of patients with refractory disease. As such, in this review we summarize the key takeaways of the latest research in the management of moderate-to-severe Crohn's disease, focusing on maximization of our currently available medications, while also exploring topics such as combination advanced therapies. We also describe evidence for emerging and alternative therapeutic modalities, including fecal microbiota transplant, exclusive enteral feeding, hyperbaric oxygen, stem cell therapy, bone marrow transplant, and posaconazole, with a focus on both the potential impact and specific indications for each.
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Affiliation(s)
- Kate E Lee
- Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Violet Y Tu
- Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Adam S Faye
- Department of Gastroenterology, New York University School of Medicine, New York, NY, USA
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41
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Kumar M, Murugesan S, Ibrahim N, Elawad M, Al Khodor S. Predictive biomarkers for anti-TNF alpha therapy in IBD patients. J Transl Med 2024; 22:284. [PMID: 38493113 PMCID: PMC10943853 DOI: 10.1186/s12967-024-05058-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 03/04/2024] [Indexed: 03/18/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition characterized by severe gut inflammation, commonly presenting as Crohn's disease, ulcerative colitis or categorized as IBD- unclassified. While various treatments have demonstrated efficacy in adult IBD patients, the advent of anti-TNF therapies has significantly revolutionized treatment outcomes and clinical management. These therapies have played a pivotal role in achieving clinical and endoscopic remission, promoting mucosal healing, averting disease progression, and diminishing the necessity for surgery. Nevertheless, not all patients exhibit positive responses to these therapies, and some may experience a loss of responsiveness over time. This review aims to present a comprehensive examination of predictive biomarkers for monitoring the therapeutic response to anti-TNF therapy in IBD patients. It will explore their limitations and clinical utilities, paving the way for a more personalized and effective therapeutic approach.
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Affiliation(s)
- Manoj Kumar
- Research Department, Sidra Medicine, Doha, Qatar
| | | | - Nazira Ibrahim
- Division of Gastroenterology, Hepatology and Nutrition, Sidra Medicine, Doha, Qatar
| | - Mamoun Elawad
- Division of Gastroenterology, Hepatology and Nutrition, Sidra Medicine, Doha, Qatar
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42
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Malik A, Liu BD, Zhu L, Kaelber D, Song G. A Comprehensive Global Population-Based Analysis on the Coexistence of Eosinophilic Esophagitis and Inflammatory Bowel Disease. Dig Dis Sci 2024; 69:892-900. [PMID: 38218734 PMCID: PMC10960894 DOI: 10.1007/s10620-024-08283-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Accepted: 01/05/2024] [Indexed: 01/15/2024]
Abstract
BACKGROUND We explored inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE) coexistence using a global dataset. Investigating their epidemiology, risks, and impact, we aimed to enhance the understanding of concurrent diagnoses and patient outcomes. METHODS A retrospective population-based cohort study was conducted using deidentified patient data from the TriNetX database (2011-2022). We estimated the incidence and prevalence of EoE in patients with IBD, including both Crohn's disease (CD) and ulcerative colitis (UC), and vice versa. Risks of select immune-mediated conditions and disease complications were compared among patients with EoE, IBD, or concurrent diagnoses. RESULTS Our results included 174,755 patients with CD; 150,774 patients with UC; and 44,714 patients with EoE. The risk of EoE was significantly higher among patients with CD (prevalence ratio [PR] 11.2) or UC (PR 8.7) compared with individuals without IBD. The risk of IBD was higher in patients with EoE (CD: PR 11.6; UC: PR 9.1) versus those without EoE. A propensity-matched analysis of IBD patients revealed that, when comparing patients with and without EoE, the relative risk of immune-mediated comorbidities was significantly greater for celiac disease, IBD-related inflammatory conditions, eczema and asthma (CD: n = 1896; UC: n = 1231; p < 0.001). Patients with a concurrent diagnosis of EoE and IBD had a higher composite risk of IBD-related complications (CD: adjusted HR (aHR) 1.14, p < 0.005; UC: aHR 1.17, p < 0.01) and lower risk of food bolus impaction (aHR 0.445, p = 0.0011). CONCLUSION Simultaneous EoE and IBD increased IBD-related complications risk, needing more treatment (glucocorticoids, biologic therapy, abdominal surgery), while reducing EoE-related issues like food bolus impaction.
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Affiliation(s)
- Alexander Malik
- Department of Medicine, Summa Health System, Northeast Ohio Medical University, Akron, OH, USA
| | - Benjamin Douglas Liu
- Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | - Liangru Zhu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - David Kaelber
- Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | - Gengqing Song
- Division of Gastroenterology & Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA.
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Velikova T, Sekulovski M, Peshevska-Sekulovska M. Immunogenicity and Loss of Effectiveness of Biologic Therapy for Inflammatory Bowel Disease Patients Due to Anti-Drug Antibody Development. Antibodies (Basel) 2024; 13:16. [PMID: 38534206 PMCID: PMC10967499 DOI: 10.3390/antib13010016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 02/12/2024] [Accepted: 02/21/2024] [Indexed: 03/28/2024] Open
Abstract
Many patients with inflammatory bowel disease (IBD) experience a loss of effectiveness to biologic therapy (i.e., anti-TNF therapy, etc.). Therefore, in addition to the adverse effects of the treatment, these patients also face failure to achieve and maintain remission. Immunogenicity, the process of production of antibodies to biological agents, is fundamental to the evolution of loss of response to treatment in IBD patients. The presence of these antibodies in patients is linked to decreased serum drug levels and inhibited biological activity. However, immunogenicity rates exhibit significant variability across inflammatory disease states, immunoassay formats, and time periods. In this review, we aimed to elucidate the immunogenicity and immune mechanisms of antibody formation to biologics, the loss of therapy response, clinical results of biological treatment for IBD from systematic reviews and meta-analyses, as well as to summarize the most recent strategies for overcoming immunogenicity and approaches for managing treatment failure in IBD.
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Affiliation(s)
- Tsvetelina Velikova
- Medical Faculty, Sofia University St. Kliment Ohridski, 1 Kozyak Str., 1407 Sofia, Bulgaria; (T.V.); (M.S.)
| | - Metodija Sekulovski
- Medical Faculty, Sofia University St. Kliment Ohridski, 1 Kozyak Str., 1407 Sofia, Bulgaria; (T.V.); (M.S.)
- Department of Anesthesiology and Intensive Care, University Hospital Lozenetz, 1 Kozyak Str., 1407 Sofia, Bulgaria
| | - Monika Peshevska-Sekulovska
- Medical Faculty, Sofia University St. Kliment Ohridski, 1 Kozyak Str., 1407 Sofia, Bulgaria; (T.V.); (M.S.)
- Department of Gastroenterology, University Hospital Lozenetz, 1407 Sofia, Bulgaria
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Napolitano D, Settanni CR, Parisio L, Orgiana N, Poscia A, Schiavoni E, Turchini L, Cascio AL, Germini F, Sblendorio E, Milani A, Patteril C, Laterza L, Lopetuso LR, Pugliese D, Papa A, Gasbarrini A, Scaldaferri F. Transition from intravenous to subcutaneous biological therapies in inflammatory bowel disease: An online survey of patients. Indian J Gastroenterol 2024; 43:215-225. [PMID: 38244138 DOI: 10.1007/s12664-023-01500-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Accepted: 12/05/2023] [Indexed: 01/22/2024]
Abstract
BACKGROUND The transition from in-hospital intravenous administration to subcutaneous therapies to treat inflammatory bowel disease (IBD) can raise some concerns among patients due to the self-administration concerns, the management of potential side effects and the overall worries related to a change of treatment. This study aimed at evaluating patients' opinion about the switch from intravenous to subcutaneous formulations and their knowledge on new available therapeutic options. METHODS We conducted a survey using a questionnaire prepared by a team of gastroenterologists and nurses working at the IBD unit. It consists of 31 items and has been divided into four sections: descriptive, commitment, knowledge and passage mode opinion. The questions were formulated in Italian and conceived according to daily consultations with patients in everyday practice, without any previous piloting or specific medical literature reference. The survey was administered to consecutive IBD patients in intravenous biological treatment; patients currently or previously treated with subcutaneous therapy were excluded. RESULTS Four hundred questionnaires were distributed to participants. As many as 311 patients (77.7%) completed the survey, while the remaining were excluded from the analysis; 155 (49.8%) patients were favorable to switch from intravenous to subcutaneous therapy, while only 78 (25.1%) disagreed. In univariate and multi-variate analysis, the approval rate for home therapy was significantly associated with the distance from the IBD center and work/family/personal commitments. Surprisingly, only a quarter of the IBD patients knew that almost all available therapeutic agents have a subcutaneous administration route. Regarding patients' opinion on the efficacy of subcutaneous administration of biological agents compared to intravenous drugs, 194 (63%) had no definite idea, while 44 (14%) believed that the effectiveness could be reduced. CONCLUSION The transition from in-hospital to subcutaneous therapeutic management of biological therapy at home was generally viewed favorably by patients, especially if they have commitments or were residents far from the IBD center.
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Affiliation(s)
- Daniele Napolitano
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, 00168, Rome, Italy.
| | | | - Laura Parisio
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, 00168, Rome, Italy
| | | | - Andrea Poscia
- Fondazione Policlinico A. Gemelli IRCCS, 00168, Rome, Italy
| | - Elisa Schiavoni
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, 00168, Rome, Italy
| | - Laura Turchini
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, 00168, Rome, Italy
| | | | | | - Elena Sblendorio
- Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Italy
| | | | | | - Lucrezia Laterza
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, 00168, Rome, Italy
| | - Loris Riccardo Lopetuso
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, 00168, Rome, Italy
| | - Daniela Pugliese
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, 00168, Rome, Italy
| | - Alfredo Papa
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, 00168, Rome, Italy
| | - Antonio Gasbarrini
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, 00168, Rome, Italy
| | - Franco Scaldaferri
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, 00168, Rome, Italy
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Constant BD, Albenberg L, Mitchel EB, De Zoeten EF, Clapp JT, Scott FI. Prior Authorizations Delay Therapy, Impact Decision-making, and Lead to Adverse Events in Inflammatory Bowel Disease: 2022 Provider Survey. Clin Gastroenterol Hepatol 2024; 22:423-426. [PMID: 37394025 DOI: 10.1016/j.cgh.2023.06.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 06/12/2023] [Accepted: 06/21/2023] [Indexed: 07/04/2023]
Affiliation(s)
- Brad D Constant
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
| | - Lindsey Albenberg
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Elana B Mitchel
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Edwin F De Zoeten
- Division of Gastroenterology and Hepatology, Department of Pediatrics, University of Colorado Anschutz School of Medicine, Children's Hospital Colorado, Digestive Health Institute, Aurora, Colorado
| | - Justin T Clapp
- Department of Anesthesiology and Critical Care, Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Frank I Scott
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Gao B, Shentu H, Sha S, Wang D, Chen X, Huang Z, Dong N, Lai H, Xu J, Zhou X. Efficacy of IL-23 inhibitors and IL-12/23 inhibitors in the induction treatment of Crohn's disease: A meta-analysis based on randomized controlled trials. Cent Eur J Immunol 2024; 48:301-310. [PMID: 38558561 PMCID: PMC10976653 DOI: 10.5114/ceji.2023.134257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 12/15/2023] [Indexed: 04/04/2024] Open
Abstract
Introduction A growing number of randomized controlled trials (RCTs) have demonstrated the effectiveness of interleukin (IL)-23 and IL-12/23 inhibitors in treating Crohn's disease (CD). This study evaluated the efficacy of IL-23 and IL-12/23 inhibitors in the induction phase for the treatment of CD. Material and methods We searched the following databases from inception until December, 2022: Medline, Embase, Web of Science and the Cochrane Library. The primary outcome was the proportion of CD patients who achieved clinical remission at the end of the induction therapy period. Secondary outcomes included clinical response, endoscopic remission, endoscopic response and normalized C-reactive protein (CRP). Results After screening, 7 RCTs were included in our study. The meta-analysis showed that, in the induction period, more patients treated with IL-23 inhibitors and IL-12/23 inhibitors achieved clinical remission than patients with placebo therapy (RR = 2.11, 95% CI: 1.83-2.44; RR = 1.94, 95% CI: 1.64-2.29; respectively). The IL-23 inhibitor group and the IL-12/23 inhibitor group showed higher clinical response rates than the placebo group (RR = 1.92, 95% CI: 1.74-2,11; RR = 1.83, 95% CI: 1.61-2.09; respectively). In addition, the IL-23 inhibitor group had a higher endoscopic remission rate and endoscopic response rate than the placebo group; the corresponding pooled RRs were 3.40 (95% CI: 2.57-4.50) and 2.65 (95% CI: 2.65-3.12), respectively. Conclusions IL-23 and IL-12/23 inhibitors were efficient methods in the induction treatment of CD.
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Affiliation(s)
- Boyang Gao
- Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Haojie Shentu
- The Medical Imaging College, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Suyong Sha
- Emergency Medical Center, Ningbo Yinzhou No. 2 Hospital, Ningbo, Zhejiang, China
| | - Dongying Wang
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Xi Chen
- The Medical Imaging College, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Zhenwei Huang
- The Medical Imaging College, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Nan Dong
- The Medical Imaging College, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Haijia Lai
- The Medical Imaging College, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Jianying Xu
- The Medical Imaging College, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Xiaoshuai Zhou
- Department of Anus & Intestine Surgery, Ningbo Yinzhou No. 2 Hospital, Ningbo, Zhejiang, China
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Hemming-Harlo M, Merras-Salmio L, Nikkonen A, Kolho KL. Drug levels of VEDOLIZUMAB in patients with pediatric-onset inflammatory bowel disease in a real-life setting. Eur J Pediatr 2024; 183:313-322. [PMID: 37878072 PMCID: PMC10858127 DOI: 10.1007/s00431-023-05255-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 09/25/2023] [Accepted: 10/03/2023] [Indexed: 10/26/2023]
Abstract
Vedolizumab (VDZ) is used off-label in pediatric inflammatory bowel disease (PIBD). There are less data on drug levels to achieve and maintain remission in children. We aimed to study vedolizumab (VDZ) trough levels in a pediatric population in a real-life setting. We traced 50 patients with PIBD receiving VDZ treatment at our hospital, reviewed their treatment protocol, trough levels, and antidrug antibodies, and compared those to fecal calprotectin (FC) levels and achievement of corticosteroid-free maintenance therapy (CF). VDZ trough level was available from 198 samples during a median follow- up of 12.6 months. Proceeding to maintenance therapy was associated with a decline in FC but not with VDZ trough levels that were comparable between patients with FC < 100 μg/g (remission), 100-1000 μg/g, or > 1000 μg/g at 3 months (mean levels of 36.8, 28.6, and 27 μg/mL, respectively p = 0.188). At 3 months, patients achieving CF (41%) and those on corticosteroids had comparable VDZ trough levels (33 vs. 27.5 μg/mL, respectively). At 6 months, the trough level was similar in groups with FC < 100 μg/g or FC > 1000 μg/g (31.5 and 27.6 μg/mL, p = 0.859). Treatment intensification did not improve the achieved CF at 12 months. None developed drug antibodies nor discontinued the therapy for an adverse event. Conclusion: VDZ was a well-tolerated and safe biologic treatment. A positive response on gut inflammation after induction predicted proceeding to maintenance therapy whereas trough levels did not. A VDZ trough level associated with clinical remission or continuing with VDZ treatment could not be determined. What is Known: • In pediatric inflammatory bowel disease, vedolizumab is still in off-label use. • The results on the relationship between drug levels of vedolizumab and clinical remission in pediatric patients are contradictory. What is New: • This real-life setting in pediatric-onset inflammatory bowel disease showed no benefit of therapy enhancement during a median follow-up of one year. • Trough levels of vedolizumab were not associated with therapy outcomes.
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Affiliation(s)
- Maria Hemming-Harlo
- Children's Hospital, Helsinki University Hospital HUS and University of Helsinki, Stenbäckinkatu 11 FI-00290 , Helsinki, Finland
| | - Laura Merras-Salmio
- Children's Hospital, Helsinki University Hospital HUS and University of Helsinki, Stenbäckinkatu 11 FI-00290 , Helsinki, Finland
| | - Anne Nikkonen
- Children's Hospital, Helsinki University Hospital HUS and University of Helsinki, Stenbäckinkatu 11 FI-00290 , Helsinki, Finland
| | - Kaija-Leena Kolho
- Children's Hospital, Helsinki University Hospital HUS and University of Helsinki, Stenbäckinkatu 11 FI-00290 , Helsinki, Finland.
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48
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Ardizzone S, Armuzzi A, Caprioli F, Castiglione F, Danese S, Daperno M, Fantini MC, Fries W, Principi MB, Savarino E, Gionchetti P. Timing of proper introduction, optimization and maintenance of anti-TNF therapy in IBD: Results from a Delphi consensus. Dig Liver Dis 2024; 56:98-105. [PMID: 37741750 DOI: 10.1016/j.dld.2023.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 08/29/2023] [Accepted: 09/06/2023] [Indexed: 09/25/2023]
Abstract
BACKGROUND Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBDs) with a rapidly growing worldwide incidence. The last decades presented rapid progress in pharmacological treatment leading in many cases to clinical and endoscopic remission, including biological treatment with anti-TNF agents. AIM The exact timing of introduction, optimization and maintenance of anti-TNF therapy in IBDs is not thoroughly covered in current guidelines. METHODS We used the Delphi panel methodology to gather the IBD experts' views and achieve consensus for clinical recommendations on introducing and maintaining anti-TNF therapy for patients with IBDs. RESULTS Twelve recommendations achieved a high level of consensus in two assessment rounds by 52 (1st round) and 47 (2nd round) IBD experts. CONCLUSION In many clinical situations, the early use of anti-TNF therapy is recommended. Nowadays, the cost-efficacy profile of anti-TNF biosimilars makes them the first-line drug in a substantial proportion of patients, thus providing the opportunity to increase access to biological therapy.
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Affiliation(s)
- Sandro Ardizzone
- Gastrointestinal Unit ASST Fatebenefratelli Sacco-University of Milan, Milan, Italy
| | - Alessandro Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy
| | - Flavio Caprioli
- Dept. of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Fabiana Castiglione
- Department of clinical medicine and surgery, AOU Federico II hospital, Naples, Italy
| | | | - Marco Daperno
- Gastroenterology Unit, AO Ordine Mauriziano of Turin, Turin, Italy
| | | | - Walter Fries
- Gastroenterology Unit, Dept. of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Maria Beatrice Principi
- Gastroenterology Unit, Dept. of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari, Bari, Italy
| | - Edoardo Savarino
- Gastroenterology Unit, AOU University of Padua, Padua, Italy - Dept. of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Paolo Gionchetti
- IBD Unit, IRCCS AOU of Bologna, Bologna, Italy; DIMEC University of Bologna, Bologna, Italy.
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49
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Ungaro RC, Naegeli AN, Choong CKC, Shan M, Zheng XS, Hunter Gibble T, Oneacre K, Colombel JF. Early Use of Biologics Reduces Healthcare Costs in Crohn's Disease: Results from a United States Population-Based Cohort. Dig Dis Sci 2024; 69:45-55. [PMID: 36920668 DOI: 10.1007/s10620-023-07906-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 02/27/2023] [Indexed: 03/16/2023]
Abstract
BACKGROUND Early initiation of biologics in moderate-to-severe Crohn's disease (CD) may significantly alter disease progression, resulting in better patient outcomes. Limited real-world data exist on the impact of early biologic use in patients with CD in the United States. AIMS We aimed to characterize biologic initiation and subsequent healthcare resource utilization (HCRU) in adults with recently diagnosed CD. METHODS Patients with CD who initiated biologic treatment within 2 years of diagnosis (index date) were identified from medical and pharmacy claims (Merative L.P. MarketScan Database from 2010 to 2016) and classified as early (≤ 12 months post-index) or late (> 12-24 months post-index) biologic initiators. Propensity score matching balanced patient characteristics up to 1 year post-index. Differences in HCRU frequency and costs 1-2 years post-index were compared between the matched groups. RESULTS After propensity score matching, 672 pairs of early and late biologic initiators were identified. Patients who initiated biologics early had fewer outpatient visits (15.5 vs 19.8, 95% confidence interval [CI] for difference: 2.7, 6.1) and lower total medical costs ($13,646.20 vs $22,180.70, 95% CI for difference: 4748.9, 12,320.1) 1-2 years post-index than late biologic initiators. Early biologic initiators had higher medication costs 1-2 years post-index ($33,766.30 vs $30,580.70, 95% CI: 546.1, 5825.1) but lower combined medical and medication costs ($47,412.50 vs $52,761.50, 95% CI: 801.5, 9896.40). CONCLUSIONS While biologic treatments are costly, patients initiating biologics sooner after diagnosis appear to have better HCRU outcomes and require fewer healthcare resources at 1-2 years post-index, potentially leading to overall cost savings.
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Affiliation(s)
- Ryan C Ungaro
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
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Degli Esposti L, Perrone V, Sangiorgi D, Saragoni S, Dovizio M, Caprioli F, Rizzello F, Daperno M, Armuzzi A. Estimation of patients affected by inflammatory bowel disease potentially eligible for biological treatment in a real-world setting. Dig Liver Dis 2024; 56:29-34. [PMID: 37147200 DOI: 10.1016/j.dld.2023.04.022] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 03/22/2023] [Accepted: 04/23/2023] [Indexed: 05/07/2023]
Abstract
BACKGROUND/AIMS This analysis estimated the number of inflammatory bowel disease (IBD) patients presenting criteria of eligibility for biological therapies in an Italian real-world setting. METHODS An observational analysis was performed on administrative databases of a sample of Local Health Units, covering 11.3% of the national population. Adult IBD patients (CD or UC) from 2010 to the end of data availability were included. Eligibility criteria for biologics were the following: Criterion A, steroid-refractory active disease; Criterion B, steroid-dependent patients; Criterion C, intolerance or contraindication to conventional therapies; Criterion D, severe relapsing disease; Criterion E (CD only), highly active CD disease and poor prognosis. RESULTS Of 26,781 IBD patient identified, 18,264 (68.2%) were treated: 3,125 (11.7%) with biologics and 15,139 (56.5%) non-biotreated. Among non-biotreated, 7,651 (28.6%) met at least one eligibility criterion for biologics, with criterion B (steroid-dependence) and criterion D (relapse) as the most represented (58-27% and 56-76%, respectively). Data reportioned to the Italian population estimated 67,635 patients as potentially eligible for biologics. CONCLUSIONS This real-world analysis showed a trend towards undertreatment with biologics in IBD patients with 28.6% being potentially eligible, suggesting that an unmet medical need still exists among the Italian general clinical practice for IBD management.
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Affiliation(s)
- Luca Degli Esposti
- CliCon S.r.l. Società Benefit Health, Economics & Outcomes Research, Bologna, Italy.
| | - Valentina Perrone
- CliCon S.r.l. Società Benefit Health, Economics & Outcomes Research, Bologna, Italy
| | - Diego Sangiorgi
- CliCon S.r.l. Società Benefit Health, Economics & Outcomes Research, Bologna, Italy
| | - Stefania Saragoni
- CliCon S.r.l. Società Benefit Health, Economics & Outcomes Research, Bologna, Italy
| | - Melania Dovizio
- CliCon S.r.l. Società Benefit Health, Economics & Outcomes Research, Bologna, Italy
| | - Flavio Caprioli
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Fernando Rizzello
- IBD Unit, DIMEC, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Marco Daperno
- Gastroeterology Unit, Mauriziano Hospital, Turin, Italy
| | - Alessandro Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
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